Is CAPG p.Arg153Trp (c.457C>T) pathogenic?

CAPG p.Arg153Trp (c.457C>T) is classified Uncertain significance in CAPG (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-13). AlphaMissense: likely benign (0.3115); Very rare (popmax 0.004%, afr).

How common is CAPG p.Arg153Trp (c.457C>T) in the general population?

CAPG p.Arg153Trp (c.457C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CAPG p.Arg153Trp (c.457C>T)?

AlphaMissense predicts likely benign (score 0.3115) — an in-silico prediction, not a clinical call.

CAPG p.Arg153Trp

c.457C>T · rs185763147 · VCV2471221

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3115 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3115	likely benign
REVEL	0.291	indeterminate
SaProt	LLR -10.88	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -1.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,249 bp · p 0.21 · regional, not allelic
Overall
CADD	26.5	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 0.004% African / African-American · 3/75,042 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00173% 28/1,614,160 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,625
African / African-Americangrpmax	0.004%	25,014
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
East Asian	0.00223%	44,882
Admixed American	0.00167%	60,020
European (non-Finnish)	0.00153%	65,556

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg153Trp
Coding: c.457C>T
MANE Select: NM_001747
dbSNP: rs185763147
Type: single nucleotide variant
Location: chr2:85401224 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.89 · 2 PDB
Residue 153: 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.Arg202Pro 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-arg153trp (accessed [today's date]).

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