Is VIM p.Asp181Ala (c.542A>C) pathogenic?

VIM p.Asp181Ala (c.542A>C) is classified Likely benign in VIM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.9162); Rare (popmax 0.321%, afr); Associated with cataract 30.

What condition is associated with VIM p.Asp181Ala (c.542A>C)?

VIM p.Asp181Ala (c.542A>C) is associated with cataract 30 (ClinVar).

How common is VIM p.Asp181Ala (c.542A>C) in the general population?

VIM p.Asp181Ala (c.542A>C) is rare (popmax 0.321%, afr) (gnomAD).

What do computational predictors say about VIM p.Asp181Ala (c.542A>C)?

AlphaMissense predicts likely pathogenic (score 0.9162) — an in-silico prediction, not a clinical call.

VIM p.Asp181Ala

c.542A>C · rs149942621 · VCV772763

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9162 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.321%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 30

Computational evidence

Protein change
AlphaMissense	0.9162	likely pathogenic
REVEL	0.805	moderately pathogenic-leaning
SaProt	LLR -13.29	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 9.1	GERP 2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 7,480 bp · p 0.038 · regional, not allelic
Overall
CADD	31.0	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 0.321% African / African-American · 241/75,058 alleles

Filtering AF 0.288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.275%

Overall 0.0231% 373/1,612,268 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.321%	311
South Asian	0.0518%	1,932
Remaining individualsnot grpmax-eligible	0.0432%	2,312
Admixed American	0.0284%	3,523
Middle Eastern	0.0165%	6,060
European (non-Finnish)	0.00339%	29,491

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.Asp181Ala
Coding: c.542A>C
MANE Select: NM_003380
dbSNP: rs149942621
Type: single nucleotide variant
Location: chr10:17229964 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 181: an α-helix; the if rod domain; the 'coil 1b' 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-asp181ala (accessed [today's date]).

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