Is VPS13C p.Val80Phe (c.238G>T) pathogenic?

VPS13C p.Val80Phe (c.238G>T) is classified Uncertain significance in VPS13C (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-24). AlphaMissense: likely benign (0.2677); Rare (popmax 0.201%, afr).

How common is VPS13C p.Val80Phe (c.238G>T) in the general population?

VPS13C p.Val80Phe (c.238G>T) is rare (popmax 0.201%, afr) (gnomAD).

What do computational predictors say about VPS13C p.Val80Phe (c.238G>T)?

AlphaMissense predicts likely benign (score 0.2677) — an in-silico prediction, not a clinical call.

VPS13C p.Val80Phe

c.238G>T · rs116290723 · VCV1362692

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2677 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.201%, afr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.2677	likely benign
REVEL	0.734	pathogenic-leaning
SaProt	—	not scored · why
⇒ REVEL calls this damaging; AlphaMissense does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	GERP 1.2, phastCons 0.92
Regional constraint	o/e 1.10	unconstrained · MANE · 191 kb · p 5.5e-11 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.201% African / African-American · 150/74,556 alleles

Filtering AF 0.175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.165%

Overall 0.00966% 155/1,603,734 alleles · rare exomes 64/1,451,752 · genomes 91/151,982 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.201%	497
Remaining individualsnot grpmax-eligible	0.00646%	15,478
Admixed American	0.00169%	59,096

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: VPS13C
Protein: p.Val80Phe
Coding: c.238G>T
MANE Select: NM_020821
dbSNP: rs116290723
Type: single nucleotide variant
Location: chr15:62035002 (GRCh38)
Gene constraint: LOEUF 0.857 · pLI <0.01 (gnomAD)
Residue 80: the chorein n-terminal domain

Full VPS13C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VPS13C c.5868+1G>A Likely pathogenic ★★ same type
VPS13C p.Arg2936Ter Pathogenic/Likely pathogenic ★★ same type
VPS13C p.Arg3652Ter Pathogenic/Likely pathogenic ★★ same type
VPS13C p.Arg371Ter Pathogenic/Likely pathogenic ★★ same type
VPS13C p.Arg567Ter Pathogenic/Likely pathogenic ★★ same type
VPS13C p.Gln3257Ter Pathogenic ★★ same type
VPS13C p.Glu3354Ter Pathogenic ★★ same type
VPS13C p.Glu3407Ter Pathogenic/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/vps13c-p-val80phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown