Is VIM p.Arg381Cys (c.1141C>T) pathogenic?

VIM p.Arg381Cys (c.1141C>T) is classified Uncertain significance in VIM (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-28). AlphaMissense: likely pathogenic (0.7068); Very rare (popmax 0.00333%, amr); Associated with cataract 30.

What condition is associated with VIM p.Arg381Cys (c.1141C>T)?

VIM p.Arg381Cys (c.1141C>T) is associated with cataract 30 (ClinVar).

How common is VIM p.Arg381Cys (c.1141C>T) in the general population?

VIM p.Arg381Cys (c.1141C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about VIM p.Arg381Cys (c.1141C>T)?

AlphaMissense predicts likely pathogenic (score 0.7068) — an in-silico prediction, not a clinical call.

VIM p.Arg381Cys

c.1141C>T · rs749084801 · VCV930366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7068 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 30

Computational evidence

Protein change
AlphaMissense	0.7068	likely pathogenic
REVEL	0.665	pathogenic-leaning
SaProt	LLR -13.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 7,480 bp · p 0.038 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00333% Admixed American · 2/60,006 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00279% 45/1,614,074 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,003
European (non-Finnish)	0.0033%	30,258
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-American	0.00133%	74,924
South Asian	0.0011%	91,088

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: VIM
Protein: p.Arg381Cys
Coding: c.1141C>T
MANE Select: NM_003380
dbSNP: rs749084801
Type: single nucleotide variant
Location: chr10:17235301 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 381: the if rod domain; the 'coil 2' region

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

Disease context

cataract 30 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VIM p.Arg381His Uncertain significance ★ ⚠ same residue
VIM p.Arg45His Uncertain significance ★★ ⚠ same condition
VIM p.Asp360Glu Uncertain significance ★★ ⚠ same condition
VIM p.Leu164Val Uncertain significance ★★ ⚠ same condition
VIM p.Thr458Ala Uncertain significance ★★ ⚠ same condition
VIM p.Val272Ile Uncertain significance ★★ ⚠ same condition
VIM c.1008+18A>G Benign/Likely benign ★★ same condition
VIM c.1009-10C>T Benign ★★ 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/vim-p-arg381cys (accessed [today's date]).

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