Is CAPZB p.Cys147Ser (c.439T>A) pathogenic?

CAPZB p.Cys147Ser (c.439T>A) is classified Uncertain significance in CAPZB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-03). AlphaMissense: likely pathogenic (0.7478); Absent from gnomAD v4.1.

How common is CAPZB p.Cys147Ser (c.439T>A) in the general population?

CAPZB p.Cys147Ser (c.439T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPZB p.Cys147Ser (c.439T>A)?

AlphaMissense predicts likely pathogenic (score 0.7478) — an in-silico prediction, not a clinical call.

CAPZB p.Cys147Ser

c.439T>A · VCV3484935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7478 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7478	likely pathogenic
REVEL	0.375	indeterminate
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 146 kb · p 2.7e-21 · regional, not allelic
Overall
CADD	22.2	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: CAPZB
Protein: p.Cys147Ser
Coding: c.439T>A
MANE Select: NM_004930
Type: single nucleotide variant
Location: chr1:19357454 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.18 · 8 PDB
Residue 147: a β-strand

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

Similar variants

CAPZB c.731+1496C>G Uncertain significance ★ ⚠ same type
CAPZB c.731+1519C>A Uncertain significance ★ same type
CAPZB c.731+1520A>G Uncertain significance ★ ⚠ same type
CAPZB c.731+1568G>A Uncertain significance ★ ⚠ same type
CAPZB p.Arg215His Uncertain significance ★ ⚠ same type
CAPZB p.Met88Val Uncertain significance ★ ⚠ same type
CAPZB p.Ser34Cys Uncertain significance ★ ⚠ same type
CAPZB p.Thr164Ile 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/capzb-p-cys147ser (accessed [today's date]).

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