VPS16 p.Phe418=
c.1254C>T · rs368671330 · VCV2652160
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0173%, nfe)
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 -9.9 | GERP -4.3 |
| Overall | ||
| CADD | 3.839 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0173%
European (non-Finnish) · 204/1,180,030 alleles
Filtering AF
0.0153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0146%
Overall
0.0137%
221/1,613,996 alleles · ultra-rare
exomes 204/1,461,838 · genomes 17/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0173% | 5,784 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,249 |
| Admixed American | 0.005% | 20,001 |
| African / African-American | 0.004% | 24,971 |
| South Asian | 0.0011% | 91,090 |
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
- VPS16
- Protein
- p.Phe418=
- Coding
- c.1254C>T
- MANE Select
- NM_022575
- dbSNP
- rs368671330
- Type
- single nucleotide variant
- Location
- chr20:2862857 (GRCh38)
- Gene constraint
- LOEUF 0.813 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.35 · 1 PDB
- Residue 418
- a UniProt-annotated variant site (in dyt30)
Similar variants
- VPS16 c.1331+2T>C Likely pathogenic ★★ same type
- VPS16 p.Arg635Ter Pathogenic ★★ same type
- VPS16 p.Tyr445Ter Pathogenic ★★ same type
- VPS16 p.Tyr463Ter Pathogenic/Likely pathogenic ★★ same type
- VPS16 c.1332-1G>T Uncertain significance ★★ same type
- VPS16 p.Arg129Gln Uncertain significance ★★ ⚠ same type
- VPS16 p.Arg262Trp Uncertain significance ★★ ⚠ same type
- VPS16 p.Arg273Cys 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/vps16-p-phe418 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown