Is VPS13C p.Phe1237Val (c.3709T>G) pathogenic?

VPS13C p.Phe1237Val (c.3709T>G) is classified Uncertain significance in VPS13C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-16). AlphaMissense: likely benign (0.1334); Very rare (popmax 0.01%, amr).

How common is VPS13C p.Phe1237Val (c.3709T>G) in the general population?

VPS13C p.Phe1237Val (c.3709T>G) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about VPS13C p.Phe1237Val (c.3709T>G)?

AlphaMissense predicts likely benign (score 0.1334) — an in-silico prediction, not a clinical call.

VPS13C p.Phe1237Val

c.3709T>G · rs140792170 · VCV2682587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1334 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1334	likely benign
REVEL	0.231	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -1.7, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 191 kb · p 5.5e-11 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,008 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00266% 43/1,614,026 alleles · very rare exomes 38/1,461,794 · genomes 5/152,232 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,001
European (non-Finnish)	0.00297%	33,713
African / African-American	0.00267%	37,501

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.Phe1237Val
Coding: c.3709T>G
MANE Select: NM_020821
dbSNP: rs140792170
Type: single nucleotide variant
Location: chr15:61961788 (GRCh38)
Gene constraint: LOEUF 0.857 · pLI <0.01 (gnomAD)

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-phe1237val (accessed [today's date]).

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