VAC14 p.Pro334=
c.1002C>T · rs16970545 · VCV1265921
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 14.7%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7 | GERP -4 |
| Overall | ||
| CADD | 0.336 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
14.7%
African / African-American · 11,016/74,986 alleles
Filtering AF
14.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 14.4%
Overall
0.841%
13,577/1,614,074 alleles · common
exomes 7,161/1,461,836 · genomes 6,416/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 14.7% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 2.68% | 37 |
| Remaining individualsnot grpmax-eligible | 1.15% | 87 |
| Admixed American | 0.773% | 129 |
| Middle Eastern | 0.495% | 202 |
| European (non-Finnish) | 0.0453% | 2,210 |
| South Asian | 0.0209% | 4,794 |
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
- VAC14
- Protein
- p.Pro334=
- Coding
- c.1002C>T
- MANE Select
- NM_018052
- dbSNP
- rs16970545
- Type
- single nucleotide variant
- Location
- chr16:70780884 (GRCh38)
- Gene constraint
- LOEUF 0.681 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.63 · 1 PDB
Similar variants
- VAC14 p.Leu308Ter Pathogenic/Likely pathogenic ★★ same type
- VAC14 p.Ala474Thr Uncertain significance ★★ ⚠ same type
- VAC14 p.Arg110His Uncertain significance ★★ ⚠ same type
- VAC14 p.Arg434Trp Uncertain significance ★★ same type
- VAC14 p.Arg438Gln Uncertain significance ★★ ⚠ same type
- VAC14 p.Arg438Trp Uncertain significance ★★ ⚠ same type
- VAC14 p.Arg623Cys Uncertain significance ★★ ⚠ same type
- VAC14 p.Arg766Gln Uncertain significance ★★ ⚠ 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/vac14-p-pro334 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown