Is VIM p.Tyr30Cys (c.89A>G) pathogenic?

VIM p.Tyr30Cys (c.89A>G) is classified Uncertain significance in VIM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely benign (0.1208); Very rare (popmax 0.00334%, amr).

How common is VIM p.Tyr30Cys (c.89A>G) in the general population?

VIM p.Tyr30Cys (c.89A>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about VIM p.Tyr30Cys (c.89A>G)?

AlphaMissense predicts likely benign (score 0.1208) — an in-silico prediction, not a clinical call.

VIM p.Tyr30Cys

c.89A>G · rs1846740908 · VCV2303431

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1208 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1208	likely benign
REVEL	0.449	indeterminate
SaProt	LLR -8.39	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 2.2	GERP -3.6, phastCons 0.78
Regional constraint	o/e 1.06	unconstrained · MANE · 255 bp · p 0.5 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,928 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000206% 3/1,455,874 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,964
African / African-American	0.00133%	74,950

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.Tyr30Cys
Coding: c.89A>G
MANE Select: NM_003380
dbSNP: rs1846740908
Type: single nucleotide variant
Location: chr10:17229511 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 30: the 'disordered' region; the 'head' 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-tyr30cys (accessed [today's date]).

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