Is VIM p.Ala89Gly (c.266C>G) pathogenic?

VIM p.Ala89Gly (c.266C>G) is classified Uncertain significance in VIM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely pathogenic (0.6155); Absent from gnomAD v4.1.

How common is VIM p.Ala89Gly (c.266C>G) in the general population?

VIM p.Ala89Gly (c.266C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VIM p.Ala89Gly (c.266C>G)?

AlphaMissense predicts likely pathogenic (score 0.6155) — an in-silico prediction, not a clinical call.

VIM p.Ala89Gly

c.266C>G · VCV4198805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6155 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6155	likely pathogenic
REVEL	0.591	indeterminate
SaProt	LLR -11.29	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 108 bp · p 9.3e-05 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: VIM
Protein: p.Ala89Gly
Coding: c.266C>G
MANE Select: NM_003380
Type: single nucleotide variant
Location: chr10:17229688 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 89: 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-ala89gly (accessed [today's date]).

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