VPS13D p.Pro3545=
c.10635C>T · rs542228203 · VCV2190803
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.436%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.286 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.12 | GERP -4.2, phastCons 0.59 |
| Overall | ||
| CADD | 7.473 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.436%
South Asian · 397/91,072 alleles
Filtering AF
0.401%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.387%
Overall
0.0272%
439/1,614,140 alleles · rare
exomes 418/1,461,892 · genomes 21/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.436% | 229 |
| Remaining individualsnot grpmax-eligible | 0.0304% | 3,290 |
| European (non-Finnish) | 0.00195% | 51,305 |
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
- VPS13D
- Protein
- p.Pro3545=
- Coding
- c.10635C>T
- MANE Select
- NM_015378
- dbSNP
- rs542228203
- Type
- single nucleotide variant
- Location
- chr1:12369529 (GRCh38)
- Gene constraint
- LOEUF 0.426 · pLI 1.00 (gnomAD)
- Residue 3545
- the shr-bd domain; a UniProt-annotated variant site (in scar4); a UniProt-annotated variant site (in scar4; altered mitochondrial morphology in patient cells); a UniProt-annotated variant site (in scar4; decreased protein abundance; altered mitochondrial morphology in patient cells)
Similar variants
- VPS13D c.941+3A>G Pathogenic/Likely pathogenic ★★ same type
- VPS13D p.Ala4139Val Likely pathogenic ★★ ⚠ same type
- VPS13D p.Arg303Ter Pathogenic/Likely pathogenic ★★ same type
- VPS13D p.Arg316Ter Pathogenic/Likely pathogenic ★★ same type
- VPS13D p.Arg3253Ter Pathogenic/Likely pathogenic ★★ same type
- VPS13D p.Arg3518Ter Likely pathogenic ★★ same type
- VPS13D p.Gly1190Asp Pathogenic/Likely pathogenic ★★ same type
- VPS13D p.Ala1265Ser 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/vps13d-p-pro3545 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown