Is VIM p.Gln204His (c.612A>C) pathogenic?

VIM p.Gln204His (c.612A>C) is classified Uncertain significance in VIM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely benign (0.1843); Very rare (popmax 0.00534%, afr).

How common is VIM p.Gln204His (c.612A>C) in the general population?

VIM p.Gln204His (c.612A>C) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about VIM p.Gln204His (c.612A>C)?

AlphaMissense predicts likely benign (score 0.1843) — an in-silico prediction, not a clinical call.

VIM p.Gln204His

c.612A>C · VCV3979750

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1843 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1843	likely benign
REVEL	0.457	indeterminate
SaProt	LLR -8.65	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 -1.9	GERP -3.7
Regional constraint	o/e 0.90	unconstrained · MANE · 7,480 bp · p 0.038 · regional, not allelic
Overall
CADD	15.18	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 0.00534% African / African-American · 4/74,922 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,613,984 alleles · very rare exomes 3/1,461,870 · genomes 1/152,114 · 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.Gln204His
Coding: c.612A>C
MANE Select: NM_003380
Type: single nucleotide variant
Location: chr10:17230698 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 78.05 · 26 PDB
Residue 204: an α-helix; the if rod domain; the 'coil 1b' 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-gln204his (accessed [today's date]).

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