Is CAPZA2 p.Trp271Ter (c.813G>A) pathogenic?

CAPZA2 p.Trp271Ter (c.813G>A) is classified Uncertain significance in CAPZA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). Absent from gnomAD v4.1.

How common is CAPZA2 p.Trp271Ter (c.813G>A) in the general population?

CAPZA2 p.Trp271Ter (c.813G>A) is absent from gnomAD v4.1 (gnomAD).

CAPZA2 p.Trp271Ter

c.813G>A · rs2486008477 · VCV2577676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CAPZA2
Protein: p.Trp271Ter
Coding: c.813G>A
MANE Select: NM_006136
dbSNP: rs2486008477
Type: single nucleotide variant
Location: chr7:116917819 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 93.11

Full CAPZA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPZA2 p.Arg259Cys Likely pathogenic ★ same type
CAPZA2 p.Lys256Glu Pathogenic ★ same type
CAPZA2 c.103+1G>A Uncertain significance ★ same type
CAPZA2 c.585+1G>T Uncertain significance ★ same type
CAPZA2 c.585+2T>G Uncertain significance ★ same type
CAPZA2 c.720+1G>A Uncertain significance ★ same type
CAPZA2 p.Ala116Thr Uncertain significance ★ ⚠ same type
CAPZA2 p.Ala130Val 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/capza2-p-trp271ter (accessed [today's date]).

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