Is CCZ1 p.Phe209Cys (c.626T>G) pathogenic?

CCZ1 p.Phe209Cys (c.626T>G) is classified Uncertain significance in CCZ1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-18). Absent from gnomAD v4.1.

How common is CCZ1 p.Phe209Cys (c.626T>G) in the general population?

CCZ1 p.Phe209Cys (c.626T>G) is absent from gnomAD v4.1 (gnomAD).

CCZ1 p.Phe209Cys

c.626T>G · rs2534767686 · VCV2476220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
REVEL	0.805	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 11 kb · p 0.00016 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

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: CCZ1
Protein: p.Phe209Cys
Coding: c.626T>G
MANE Select: NM_015622
dbSNP: rs2534767686
Type: single nucleotide variant
Location: chr7:5905197 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 89.12 · 1 PDB
Residue 209: an α-helix

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-phe209cys (accessed [today's date]).

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