VAC14 p.Asp686=
c.2058C>T · rs568088943 · VCV1919422
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0421%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.2 | GERP -2.8 |
| Overall | ||
| CADD | 7.176 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0421%
South Asian · 38/90,276 alleles
Filtering AF
0.0315%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0278%
Overall
0.00298%
48/1,611,210 alleles · ultra-rare
exomes 42/1,458,884 · genomes 6/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0421% | 2,376 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00341% | 29,308 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,200 |
| East Asian | 0.00223% | 44,826 |
| European (non-Finnish) | 0.000509% | 196,576 |
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.Asp686=
- Coding
- c.2058C>T
- MANE Select
- NM_018052
- dbSNP
- rs568088943
- Type
- single nucleotide variant
- Location
- chr16:70692949 (GRCh38)
- Gene constraint
- LOEUF 0.681 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.63 · 1 PDB
Similar variants
- VAC14 p.Asp686Gly Uncertain significance ★ ⚠ same residue
- 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
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-asp686 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown