VPS13A p.Ser751=
c.2253T>G · rs937699726 · VCV1157276
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00266%, afr)
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 -0.94 | GERP -2.1, phastCons 0.005 |
| Overall | ||
| CADD | 8.399 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00266%
African / African-American · 2/75,050 alleles
Filtering AF
0.000442%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000186%
3/1,614,012 alleles · very rare
exomes 3/1,461,710 · genomes 0/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00266% | 37,525 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,502 |
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
- VPS13A
- Protein
- p.Ser751=
- Coding
- c.2253T>G
- MANE Select
- NM_033305
- dbSNP
- rs937699726
- Type
- single nucleotide variant
- Location
- chr9:77252317 (GRCh38)
- Gene constraint
- LOEUF 0.696 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 751
- a UniProt-annotated variant site (in chac)
Similar variants
- VPS13A p.Ser751Phe Uncertain significance ★ ⚠ same residue
- VPS13A p.Ser751fs Pathogenic ★ same residue
- VPS13A c.144+1G>C Pathogenic ★★ same type
- VPS13A c.1596-1G>C Pathogenic/Likely pathogenic ★★ same type
- VPS13A c.1596-2A>G Pathogenic ★★ same type
- VPS13A c.188-2A>G Likely pathogenic ★★ same type
- VPS13A c.2037+1G>A Likely pathogenic ★★ same type
- VPS13A c.2427+1G>A Likely pathogenic ★★ 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/vps13a-p-ser751 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown