Is CCZ1 p.Ile210Phe (c.628A>T) pathogenic?

CCZ1 p.Ile210Phe (c.628A>T) is classified Uncertain significance in CCZ1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). Very rare (popmax 0.000779%, nfe).

How common is CCZ1 p.Ile210Phe (c.628A>T) in the general population?

CCZ1 p.Ile210Phe (c.628A>T) is very rare (popmax 0.000779%, nfe) (gnomAD).

CCZ1 p.Ile210Phe

c.628A>T · VCV4222464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000779%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.29	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 11 kb · p 0.00016 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000779% European (non-Finnish) · 9/1,154,966 alleles

Filtering AF 0.000367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000266%

Overall 0.000773% 11/1,422,752 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0033%	30,341
European (non-Finnish)grpmax	0.000779%	128,330

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile210Phe
Coding: c.628A>T
MANE Select: NM_015622
Type: single nucleotide variant
Location: chr7:5905199 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 89.12 · 1 PDB
Residue 210: 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-ile210phe (accessed [today's date]).

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