Is CAPZA1 p.Arg15Cys (c.43C>T) pathogenic?

CAPZA1 p.Arg15Cys (c.43C>T) is classified Uncertain significance in CAPZA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: ambiguous (0.5161); Very rare (popmax 0.00711%, eas).

How common is CAPZA1 p.Arg15Cys (c.43C>T) in the general population?

CAPZA1 p.Arg15Cys (c.43C>T) is very rare (popmax 0.00711%, eas) (gnomAD).

What do computational predictors say about CAPZA1 p.Arg15Cys (c.43C>T)?

AlphaMissense predicts ambiguous (score 0.5161) — an in-silico prediction, not a clinical call.

CAPZA1 p.Arg15Cys

c.43C>T · rs763035612 · VCV2476607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5161 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00711%, eas)

Computational evidence

Protein change
AlphaMissense	0.5161	ambiguous
REVEL	0.412	indeterminate
SaProt	LLR -11.32	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.8	GERP 2.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 34 kb · p 0.33 · regional, not allelic
Overall
CADD	25.8	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 0.00711% East Asian · 3/42,180 alleles

Filtering AF 0.00189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00102%

Overall 0.00152% 23/1,510,422 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00711%	14,060
Admixed American	0.00555%	18,011
European (non-Finnish)	0.00143%	69,753
South Asian	0.00134%	74,362

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: CAPZA1
Protein: p.Arg15Cys
Coding: c.43C>T
MANE Select: NM_006135
dbSNP: rs763035612
Type: single nucleotide variant
Location: chr1:112647213 (GRCh38)
Gene constraint: LOEUF 0.329 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 93.19 · 10 PDB
Residue 15: an α-helix

Full CAPZA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPZA1 c.506+1G>C Uncertain significance ★ same type
CAPZA1 p.Ala50Ser Uncertain significance ★ ⚠ same type
CAPZA1 p.Arg172His Uncertain significance ★ ⚠ same type
CAPZA1 p.Asn138Ser Uncertain significance ★ ⚠ same type
CAPZA1 p.Asn34Ser Uncertain significance ★ ⚠ same type
CAPZA1 p.Asp10Ala Uncertain significance ★ ⚠ same type
CAPZA1 p.Asp211Glu Uncertain significance ★ ⚠ same type
CAPZA1 p.Asp214His 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/capza1-p-arg15cys (accessed [today's date]).

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