Is CAPG p.Pro31Leu (c.92C>T) pathogenic?

CAPG p.Pro31Leu (c.92C>T) is classified Uncertain significance in CAPG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-12). AlphaMissense: likely benign (0.2651); Ultra-rare (popmax 0.0495%, mid).

How common is CAPG p.Pro31Leu (c.92C>T) in the general population?

CAPG p.Pro31Leu (c.92C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about CAPG p.Pro31Leu (c.92C>T)?

AlphaMissense predicts likely benign (score 0.2651) — an in-silico prediction, not a clinical call.

CAPG p.Pro31Leu

c.92C>T · rs140150295 · VCV3137012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2651 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2651	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -8.76	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 8.6	GERP 0.25, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,249 bp · p 0.21 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.0031% 50/1,613,938 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
African / African-American	0.0107%	9,368
South Asian	0.00439%	22,769
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.00263%	38,064
East Asian	0.00223%	44,866
Admixed American	0.00167%	60,002

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.Pro31Leu
Coding: c.92C>T
MANE Select: NM_001747
dbSNP: rs140150295
Type: single nucleotide variant
Location: chr2:85401889 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.89 · 2 PDB
Residue 31: 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-pro31leu (accessed [today's date]).

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