Is CAPG p.Val208Met (c.622G>A) pathogenic?

CAPG p.Val208Met (c.622G>A) is classified Uncertain significance in CAPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: ambiguous (0.3818); Very rare (popmax 0.00167%, amr).

How common is CAPG p.Val208Met (c.622G>A) in the general population?

CAPG p.Val208Met (c.622G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CAPG p.Val208Met (c.622G>A)?

AlphaMissense predicts ambiguous (score 0.3818) — an in-silico prediction, not a clinical call.

CAPG p.Val208Met

c.622G>A · VCV4218721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3818 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3818	ambiguous
REVEL	0.153	moderately benign-leaning
SaProt	LLR -12.14	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.36	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,249 bp · p 0.21 · regional, not allelic
Overall
CADD	24.7	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 0.00167% Admixed American · 1/60,016 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000681% 11/1,614,144 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,016
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000763%	131,116

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.Val208Met
Coding: c.622G>A
MANE Select: NM_001747
Type: single nucleotide variant
Location: chr2:85399180 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.89 · 2 PDB
Residue 208: 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-val208met (accessed [today's date]).

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