Is VPS13C p.Ile3726Val (c.11176A>G) pathogenic?

VPS13C p.Ile3726Val (c.11176A>G) is classified Benign/Likely benign in VPS13C (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.0796); Rare (popmax 0.792%, mid).

How common is VPS13C p.Ile3726Val (c.11176A>G) in the general population?

VPS13C p.Ile3726Val (c.11176A>G) is rare (popmax 0.792%, mid) (gnomAD).

What do computational predictors say about VPS13C p.Ile3726Val (c.11176A>G)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

VPS13C p.Ile3726Val

c.11176A>G · rs115819951 · VCV791595

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.792%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.198	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 5.1	GERP 2.3, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 15 kb · p 0.079 · regional, not allelic
Overall
CADD	20.7	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 0.792% Middle Eastern · 48/6,062 alleles

Filtering AF 0.614% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.55%

Overall 0.473% 7,630/1,614,094 alleles · rare exomes 7,116/1,461,780 · genomes 514/152,314 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.792%	126
Ashkenazi Jewishnot grpmax-eligible	0.669%	150
European (non-Finnish)	0.557%	179
Remaining individualsnot grpmax-eligible	0.502%	199
Admixed American	0.27%	370
Amishnot grpmax-eligible	0.219%	456
Finnishnot grpmax-eligible	0.151%	660
South Asian	0.149%	670
African / African-American	0.128%	782
East Asian	0.00446%	22,440

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.Ile3726Val
Coding: c.11176A>G
MANE Select: NM_020821
dbSNP: rs115819951
Type: single nucleotide variant
Location: chr15:61854543 (GRCh38)
Gene constraint: LOEUF 0.857 · pLI <0.01 (gnomAD)
Residue 3726: the 'required for lipid droplet localization' region

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-ile3726val (accessed [today's date]).

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