Is CAPZA2 p.Ala55Val (c.164C>T) pathogenic?

CAPZA2 p.Ala55Val (c.164C>T) is classified Uncertain significance in CAPZA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely pathogenic (0.8005); Absent from gnomAD v4.1.

How common is CAPZA2 p.Ala55Val (c.164C>T) in the general population?

CAPZA2 p.Ala55Val (c.164C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPZA2 p.Ala55Val (c.164C>T)?

AlphaMissense predicts likely pathogenic (score 0.8005) — an in-silico prediction, not a clinical call.

CAPZA2 p.Ala55Val

c.164C>T · VCV3769673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8005 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8005	likely pathogenic
REVEL	0.681	pathogenic-leaning
SaProt	LLR -9.83	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 55 kb · p 2.8e-07 · regional, not allelic
Overall
CADD	27.9	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

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.Ala55Val
Coding: c.164C>T
MANE Select: NM_006136
Type: single nucleotide variant
Location: chr7:116898780 (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-ala55val (accessed [today's date]).

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