`mapped_variants.hgvs_p` stores non-protein HGVS for UTR variants

[davereinhart]

Summary

For variants outside the CDS, MappedVariant.hgvs_p is populated with a nucleotide-style expression carrying a protein accession, such as NP_078951.2:n.*21C>T. This is not valid protein HGVS. The value propagates to the CSV exports (mavedb.post_mapped_hgvs_p) and to the score set view in mavedb-ui, where it renders as a variant label and in histogram tooltips.

Reproduction

curl 'https://reg.genome.network/allele?hgvs=NM_024675.4:c.*21C>T'

The MANE RefSeq transcript allele in the response:

{
  "hgvs": ["NM_024675.4:c.*21C>T"],
  "proteinEffect": { "hgvs": "NP_078951.2:n.*21C>T" },
  "MANE": {
    "nucleotide": { "RefSeq": { "hgvs": "NM_024675.4:c.*21C>T" } },
    "protein":    { "RefSeq": { "hgvs": "NP_078951.2:n.*21C>T" } }
  }
}

ClinGen synthesizes a pseudo-protein expression for positions with no amino-acid consequence: the NP accession paired with the transcript-relative coordinate and an n. prefix. Every UTR variant in an affected score set has this shape.

Root cause

src/mavedb/lib/clingen/allele_registry.py::extract_hgvs_from_ca_allele_data copies ClinGen's value into hgvs_p without checking that it is a p. expression. Both branches are affected:

# transcript_accession branch
if hgvs_c:
    if allele.get("proteinEffect"):
        hgvs_p = allele["proteinEffect"].get("hgvs")
    break

# MANE fallback branch
hgvs_p = allele["MANE"].get("protein", {}).get("RefSeq", {}).get("hgvs")

extract_hgvs_from_pa_allele_data has the same gap, taking aminoAcidAlleles[0]["hgvs"][0] unvalidated.

The value is written to the database by src/mavedb/worker/jobs/external_services/hgvs.py::populate_hgvs_for_score_set:

mapped_variant.hgvs_g = hgvs_g
mapped_variant.hgvs_c = hgvs_c
mapped_variant.hgvs_p = hgvs_p

Suggested fix

src/mavedb/lib/variants.py already defines the needed predicate, is_hgvs_p (re.compile(r"(^|:)p\.")), currently used only as a CSV fallback filter. Apply it at extraction time in all three places:

hgvs_p = allele["proteinEffect"].get("hgvs")
if hgvs_p and not is_hgvs_p(hgvs_p):
    hgvs_p = None

Consider the same treatment for hgvs_c (c./n.) and hgvs_g (g.) so the columns are self-describing by construction.

Follow-up

1. A backfill is needed for rows already written. A WHERE hgvs_p IS NOT NULL AND hgvs_p NOT LIKE '%:p.%' scan will size the impact.
2. src/mavedb/lib/csv/specs.py::_post_mapped_hgvs_p returns mapping.hgvs_p unchecked and only validates the VRS fallback path. Consider validating the stored column too, as defense in depth.

Affected surfaces

• GET /score-sets/{urn}/variants/data and the annotations CSV (mavedb.post_mapped_hgvs_p)
• v_variant_annotations.hgvs_p
• mavedb-ui score set view: variant search labels and histogram tooltips