SEC31A p.Ala985=
c.2955G>A · VCV4967522
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0174%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.127 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -1.5 | GERP -3.3 |
| Overall | ||
| CADD | 11.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0174%
Middle Eastern · 1/5,738 alleles
Filtering AF
0.00935%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00741%
Overall
0.00673%
105/1,560,288 alleles · ultra-rare
exomes 98/1,408,160 · genomes 7/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0174% | 5,738 |
| South Asian | 0.0159% | 6,288 |
| African / African-American | 0.0122% | 8,184 |
| European (non-Finnish) | 0.00668% | 14,963 |
| Finnishnot grpmax-eligible | 0.00485% | 20,611 |
| East Asian | 0.00225% | 44,452 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,186 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SEC31A
- Protein
- p.Ala985=
- Coding
- c.2955G>A
- MANE Select
- NM_001077207
- Type
- single nucleotide variant
- Location
- chr4:82842153 (GRCh38)
- Gene constraint
- LOEUF 0.542 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 68.95 · 2 PDB
- Residue 985
- the 'interaction with pdcd6' region; the 'disordered' region
Similar variants
- SEC31A p.Ala985Val Uncertain significance ★ ⚠ same residue
- SEC31A p.Arg486His Uncertain significance ★★ same type
- SEC31A p.Asp84Gly Uncertain significance ★★ ⚠ same type
- SEC31A p.Cys458Trp Uncertain significance ★★ ⚠ same type
- SEC31A p.Pro945Ser Uncertain significance ★★ ⚠ same type
- SEC31A c.1045-26G>T Benign ★★ same type
- SEC31A c.2154+36G>C Benign ★★ same type
- SEC31A c.2154+8C>T Likely benign ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/sec31a-p-ala985 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown