Is VIM p.Gln250Arg (c.749A>G) pathogenic?

VIM p.Gln250Arg (c.749A>G) is classified Likely benign in VIM (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-06). AlphaMissense: likely benign (0.1061); Rare (popmax 0.357%, afr); Associated with cataract 30.

What condition is associated with VIM p.Gln250Arg (c.749A>G)?

VIM p.Gln250Arg (c.749A>G) is associated with cataract 30 (ClinVar).

How common is VIM p.Gln250Arg (c.749A>G) in the general population?

VIM p.Gln250Arg (c.749A>G) is rare (popmax 0.357%, afr) (gnomAD).

What do computational predictors say about VIM p.Gln250Arg (c.749A>G)?

AlphaMissense predicts likely benign (score 0.1061) — an in-silico prediction, not a clinical call.

VIM p.Gln250Arg

c.749A>G · rs145152785 · VCV772056

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1061 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.357%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cataract 30

Computational evidence

Protein change
AlphaMissense	0.1061	likely benign
REVEL	0.637	indeterminate
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 7,480 bp · p 0.038 · regional, not allelic
Overall
CADD	24.8	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 0.357% African / African-American · 268/75,056 alleles

Filtering AF 0.322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.308%

Overall 0.0188% 304/1,614,226 alleles · rare exomes 146/1,461,892 · genomes 158/152,334 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.357%	280
Remaining individualsnot grpmax-eligible	0.0304%	3,290
Admixed American	0.02%	5,002
South Asian	0.0011%	91,090
European (non-Finnish)	0.000339%	295,010

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.Gln250Arg
Coding: c.749A>G
MANE Select: NM_003380
dbSNP: rs145152785
Type: single nucleotide variant
Location: chr10:17233798 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 250: the if rod domain; the 'linker 12' 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-gln250arg (accessed [today's date]).

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