Is VIM p.Arg345His (c.1034G>A) pathogenic?

VIM p.Arg345His (c.1034G>A) is classified Uncertain significance in VIM (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.1173); Ultra-rare (popmax 0.0446%, eas).

How common is VIM p.Arg345His (c.1034G>A) in the general population?

VIM p.Arg345His (c.1034G>A) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

What do computational predictors say about VIM p.Arg345His (c.1034G>A)?

AlphaMissense predicts likely benign (score 0.1173) — an in-silico prediction, not a clinical call.

VIM p.Arg345His

c.1034G>A · rs116370722 · VCV1049635

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1173 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1173	likely benign
REVEL	0.587	indeterminate
SaProt	LLR -10.52	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 7,480 bp · p 0.038 · regional, not allelic
Overall
CADD	26.4	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 0.0446% East Asian · 20/44,892 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00409% 66/1,614,214 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,245
South Asian	0.0198%	5,060
Remaining individualsnot grpmax-eligible	0.0064%	15,627
African / African-American	0.00266%	37,525
European (non-Finnish)	0.00178%	56,192
Admixed American	0.00167%	60,030

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.Arg345His
Coding: c.1034G>A
MANE Select: NM_003380
dbSNP: rs116370722
Type: single nucleotide variant
Location: chr10:17235194 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 345: the if rod domain; the 'coil 2' region

Full VIM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VIM p.Arg45His Uncertain significance ★★ ⚠ same type
VIM p.Asp360Glu Uncertain significance ★★ ⚠ same type
VIM p.Leu164Val Uncertain significance ★★ ⚠ same type
VIM p.Thr458Ala Uncertain significance ★★ ⚠ same type
VIM p.Val272Ile Uncertain significance ★★ ⚠ same type
VIM c.1008+18A>G Benign/Likely benign ★★ same type
VIM c.1008+99G>A Benign ★★ same type
VIM c.1009-10C>T Benign ★★ same type

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-arg345his (accessed [today's date]).

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