Is CAPG p.Lys227Arg (c.680A>G) pathogenic?

CAPG p.Lys227Arg (c.680A>G) is classified Benign in CAPG (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-11). AlphaMissense: likely benign (0.1215); Low-frequency (popmax 3.84%, eas).

How common is CAPG p.Lys227Arg (c.680A>G) in the general population?

CAPG p.Lys227Arg (c.680A>G) is low-frequency (popmax 3.84%, eas) (gnomAD).

What do computational predictors say about CAPG p.Lys227Arg (c.680A>G)?

AlphaMissense predicts likely benign (score 0.1215) — an in-silico prediction, not a clinical call.

CAPG p.Lys227Arg

c.680A>G · rs117284777 · VCV731207

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1215 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.84%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1215	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,249 bp · p 0.21 · regional, not allelic
Overall
CADD	21.3	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 3.84% East Asian · 1,717/44,682 alleles

Filtering AF 3.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.63%

Overall 0.12% 1,933/1,604,810 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	3.84%	26
Remaining individualsnot grpmax-eligible	0.175%	570
South Asian	0.0819%	1,221
Admixed American	0.0102%	9,767
European (non-Finnish)	0.00238%	41,992

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.Lys227Arg
Coding: c.680A>G
MANE Select: NM_001747
dbSNP: rs117284777
Type: single nucleotide variant
Location: chr2:85398769 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.89 · 2 PDB

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

Similar variants

CAPG p.Lys227Glu 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-lys227arg (accessed [today's date]).

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