Is CAPG p.Arg96Cys (c.286C>T) pathogenic?

CAPG p.Arg96Cys (c.286C>T) is classified Uncertain significance in CAPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-15). AlphaMissense: likely pathogenic (0.6093); Ultra-rare (popmax 0.0329%, sas).

How common is CAPG p.Arg96Cys (c.286C>T) in the general population?

CAPG p.Arg96Cys (c.286C>T) is ultra-rare (popmax 0.0329%, sas) (gnomAD).

What do computational predictors say about CAPG p.Arg96Cys (c.286C>T)?

AlphaMissense predicts likely pathogenic (score 0.6093) — an in-silico prediction, not a clinical call.

CAPG p.Arg96Cys

c.286C>T · rs750346858 · VCV2523500

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6093 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6093	likely pathogenic
REVEL	0.729	pathogenic-leaning
SaProt	LLR -14.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,249 bp · p 0.21 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.0329% South Asian · 30/91,086 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.00291% 47/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0329%	3,036
East Asian	0.00223%	44,890
Remaining individualsnot grpmax-eligible	0.0016%	62,486
Finnishnot grpmax-eligible	0.00156%	64,016
European (non-Finnish)	0.00119%	84,288

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.Arg96Cys
Coding: c.286C>T
MANE Select: NM_001747
dbSNP: rs750346858
Type: single nucleotide variant
Location: chr2:85401594 (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.Arg96His 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-arg96cys (accessed [today's date]).

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