Is CAPG p.Arg96His (c.287G>A) pathogenic?

CAPG p.Arg96His (c.287G>A) is classified Uncertain significance in CAPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: ambiguous (0.4455); Ultra-rare (popmax 0.0111%, eas).

How common is CAPG p.Arg96His (c.287G>A) in the general population?

CAPG p.Arg96His (c.287G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about CAPG p.Arg96His (c.287G>A)?

AlphaMissense predicts ambiguous (score 0.4455) — an in-silico prediction, not a clinical call.

CAPG p.Arg96His

c.287G>A · VCV4218718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4455 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Computational evidence

Protein change
AlphaMissense	0.4455	ambiguous
REVEL	0.607	indeterminate
SaProt	LLR -13.79	damaging
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	32.0	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 0.0111% East Asian · 5/44,888 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00143% 23/1,614,014 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,978
South Asian	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00267%	37,471
European (non-Finnish)	0.000932%	107,271

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.Arg96His
Coding: c.287G>A
MANE Select: NM_001747
Type: single nucleotide variant
Location: chr2:85401593 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.89 · 2 PDB
Residue 96: a β-strand

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

Similar variants

CAPG p.Arg96Cys Uncertain significance ★ ⚠ same residue
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

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-arg96his (accessed [today's date]).

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