Is VIM p.Arg304Gln (c.911G>A) pathogenic?

VIM p.Arg304Gln (c.911G>A) is classified Uncertain significance in VIM (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-03). AlphaMissense: likely benign (0.2579); Ultra-rare (popmax 0.045%, amr); Associated with cataract 30.

What condition is associated with VIM p.Arg304Gln (c.911G>A)?

VIM p.Arg304Gln (c.911G>A) is associated with cataract 30 (ClinVar).

How common is VIM p.Arg304Gln (c.911G>A) in the general population?

VIM p.Arg304Gln (c.911G>A) is ultra-rare (popmax 0.045%, amr) (gnomAD).

What do computational predictors say about VIM p.Arg304Gln (c.911G>A)?

AlphaMissense predicts likely benign (score 0.2579) — an in-silico prediction, not a clinical call.

VIM p.Arg304Gln

c.911G>A · rs552165238 · VCV1051392

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2579 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

cataract 30

Computational evidence

Protein change
AlphaMissense	0.2579	likely benign
REVEL	0.561	indeterminate
SaProt	LLR -12.00	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.9, 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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.045% Admixed American · 27/60,016 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00762% 123/1,614,046 alleles · ultra-rare exomes 92/1,461,844 · genomes 31/152,202 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,223
Remaining individualsnot grpmax-eligible	0.008%	12,501
European (non-Finnish)	0.00737%	13,563
African / African-American	0.004%	25,003
Finnishnot grpmax-eligible	0.00156%	63,954

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.Arg304Gln
Coding: c.911G>A
MANE Select: NM_003380
dbSNP: rs552165238
Type: single nucleotide variant
Location: chr10:17234721 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 304: an α-helix; 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.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
VIM c.1360-18G>T Likely 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-arg304gln (accessed [today's date]).

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