Is CCZ1 p.Ile232Val (c.694A>G) pathogenic?

CCZ1 p.Ile232Val (c.694A>G) is classified Uncertain significance in CCZ1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). Ultra-rare (popmax 0.0125%, sas).

How common is CCZ1 p.Ile232Val (c.694A>G) in the general population?

CCZ1 p.Ile232Val (c.694A>G) is ultra-rare (popmax 0.0125%, sas) (gnomAD).

CCZ1 p.Ile232Val

c.694A>G · VCV4222467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0125%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.115	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 11 kb · p 0.00016 · regional, not allelic
Overall
CADD	19.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0125% South Asian · 10/80,308 alleles

Filtering AF 0.00668% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00507%

Overall 0.0008% 12/1,499,836 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0125%	8,031
Remaining individualsnot grpmax-eligible	0.00344%	29,034

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: CCZ1
Protein: p.Ile232Val
Coding: c.694A>G
MANE Select: NM_015622
Type: single nucleotide variant
Location: chr7:5905265 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 89.12 · 1 PDB
Residue 232: a β-strand

Full CCZ1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCZ1 p.Ala224Ser Uncertain significance ★ same type
CCZ1 p.Ala224Val Uncertain significance ★ same type
CCZ1 p.Ala4Val Uncertain significance ★ same type
CCZ1 p.Arg174Gln Uncertain significance ★ same type
CCZ1 p.Arg174Trp Uncertain significance ★ same type
CCZ1 p.Arg269Lys Uncertain significance ★ same type
CCZ1 p.Arg340Gln Uncertain significance ★ same type
CCZ1 p.Arg446Trp 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/ccz1-p-ile232val (accessed [today's date]).

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