Is VIM p.Glu151Lys (c.451G>A) pathogenic?

VIM p.Glu151Lys (c.451G>A) is classified Pathogenic in VIM (ClinVar, No assertion criteria, 2 submitters; last evaluated 2009-03-15). AlphaMissense: ambiguous (0.5096); Very rare (popmax 0.00332%, sas); Associated with cataract 30.

What condition is associated with VIM p.Glu151Lys (c.451G>A)?

VIM p.Glu151Lys (c.451G>A) is associated with cataract 30 (ClinVar).

How common is VIM p.Glu151Lys (c.451G>A) in the general population?

VIM p.Glu151Lys (c.451G>A) is very rare (popmax 0.00332%, sas) (gnomAD).

What do computational predictors say about VIM p.Glu151Lys (c.451G>A)?

AlphaMissense predicts ambiguous (score 0.5096) — an in-silico prediction, not a clinical call.

VIM p.Glu151Lys

c.451G>A · rs121917775 · VCV12199

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5096 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00332%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

cataract 30

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.5096	ambiguous
REVEL	0.865	moderately pathogenic-leaning
SaProt	LLR -12.18	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 0.07, 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 0.00332% South Asian · 3/90,330 alleles

Filtering AF 0.000882% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000606%

Overall 0.00112% 18/1,610,420 alleles · very rare exomes 16/1,458,170 · genomes 2/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00332%	30,110
European (non-Finnish)	0.00127%	78,582

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.Glu151Lys
Coding: c.451G>A
MANE Select: NM_003380
dbSNP: rs121917775
Type: single nucleotide variant
Location: chr10:17229873 (GRCh38)

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

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-glu151lys (accessed [today's date]).

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