Is CAPG p.Glu97Gln (c.289G>C) pathogenic?

CAPG p.Glu97Gln (c.289G>C) is classified Uncertain significance in CAPG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely pathogenic (0.6953); Very rare (popmax 0.00178%, nfe).

How common is CAPG p.Glu97Gln (c.289G>C) in the general population?

CAPG p.Glu97Gln (c.289G>C) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about CAPG p.Glu97Gln (c.289G>C)?

AlphaMissense predicts likely pathogenic (score 0.6953) — an in-silico prediction, not a clinical call.

CAPG p.Glu97Gln

c.289G>C · rs764009099 · VCV2305688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6953	likely pathogenic
REVEL	0.211	benign-leaning
SaProt	LLR -11.61	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,249 bp · p 0.21 · regional, not allelic
Overall
CADD	22.8	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 0.00178% European (non-Finnish) · 21/1,180,036 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0015% 22/1,461,868 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,192
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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: CAPG
Protein: p.Glu97Gln
Coding: c.289G>C
MANE Select: NM_001747
dbSNP: rs764009099
Type: single nucleotide variant
Location: chr2:85401591 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.89 · 2 PDB
Residue 97: a β-strand

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

Similar variants

CAPG p.Ala206Thr Uncertain significance ★ ⚠ same type
CAPG p.Ala229Thr Uncertain significance ★ ⚠ same type
CAPG p.Ala241Gly Uncertain significance ★ ⚠ same type
CAPG p.Ala81Pro Uncertain significance ★ ⚠ same type
CAPG p.Arg112Trp Uncertain significance ★ ⚠ same type
CAPG p.Arg149Cys Uncertain significance ★ ⚠ same type
CAPG p.Arg149Ser Uncertain significance ★ ⚠ same type
CAPG p.Arg153Trp Uncertain significance ★ ⚠ 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/capg-p-glu97gln (accessed [today's date]).

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