Is VIM p.Arg45His (c.134G>A) pathogenic?

VIM p.Arg45His (c.134G>A) is classified Uncertain significance in VIM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-14). AlphaMissense: likely benign (0.2294); Very rare (popmax 0.00502%, amr); Associated with cataract 30.

What condition is associated with VIM p.Arg45His (c.134G>A)?

VIM p.Arg45His (c.134G>A) is associated with cataract 30 (ClinVar).

How common is VIM p.Arg45His (c.134G>A) in the general population?

VIM p.Arg45His (c.134G>A) is very rare (popmax 0.00502%, amr) (gnomAD).

What do computational predictors say about VIM p.Arg45His (c.134G>A)?

AlphaMissense predicts likely benign (score 0.2294) — an in-silico prediction, not a clinical call.

VIM p.Arg45His

c.134G>A · rs778098458 · VCV1353044

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2294 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

cataract 30

Computational evidence

Protein change
AlphaMissense	0.2294	likely benign
REVEL	0.525	indeterminate
SaProt	LLR -10.07	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 255 bp · p 0.5 · regional, not allelic
Overall
CADD	24.5	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 0.00502% Admixed American · 3/59,796 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000187% 3/1,607,132 alleles · very rare exomes 3/1,454,924 · genomes 0/152,208 · joint denominator

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.Arg45His
Coding: c.134G>A
MANE Select: NM_003380
dbSNP: rs778098458
Type: single nucleotide variant
Location: chr10:17229556 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 45: the 'head' 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.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
VIM c.720+18C>T Benign/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-arg45his (accessed [today's date]).

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