Is VPS41 p.Ile232Val (c.694A>G) pathogenic?

VPS41 p.Ile232Val (c.694A>G) is classified Uncertain significance in VPS41 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.0676); Very rare (popmax 0.00551%, nfe); Associated with Inborn genetic diseases.

What condition is associated with VPS41 p.Ile232Val (c.694A>G)?

VPS41 p.Ile232Val (c.694A>G) is associated with Inborn genetic diseases (ClinVar).

How common is VPS41 p.Ile232Val (c.694A>G) in the general population?

VPS41 p.Ile232Val (c.694A>G) is very rare (popmax 0.00551%, nfe) (gnomAD).

What do computational predictors say about VPS41 p.Ile232Val (c.694A>G)?

AlphaMissense predicts likely benign (score 0.0676) — an in-silico prediction, not a clinical call.

VPS41 p.Ile232Val

c.694A>G · rs371042465 · VCV3188972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0676 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00551%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0676	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -8.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 183 kb · p 5.8e-06 · regional, not allelic
Overall
CADD	18.47	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00551% European (non-Finnish) · 65/1,179,086 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00404%

Overall 0.00428% 69/1,612,158 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00551%	18,140
Remaining individualsnot grpmax-eligible	0.00481%	20,792
African / African-American	0.00134%	74,770

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: VPS41
Protein: p.Ile232Val
Coding: c.694A>G
MANE Select: NM_014396
dbSNP: rs371042465
Type: single nucleotide variant
Location: chr7:38795488 (GRCh38)
Gene constraint: LOEUF 0.904 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 232: the 'interaction with arl8b' region

Full VPS41 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VPS41 p.Arg208Trp Uncertain significance ★★ ⚠ same condition
VPS41 p.Ile464Thr Uncertain significance ★★ ⚠ same condition
VPS41 p.Lys841Glu Uncertain significance ★★ ⚠ same condition
VPS41 p.Phe123Ser Uncertain significance ★★ ⚠ same condition
VPS41 p.Val539Ile Uncertain significance ★★ ⚠ same condition
VPS41 c.2405-5G>T Uncertain significance ★ same condition
VPS41 c.571-1G>A Uncertain significance ★ same condition
VPS41 p.Ala187Val Uncertain significance ★ ⚠ same condition

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/vps41-p-ile232val (accessed [today's date]).

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