Is CCZ1B p.Pro21Ser (c.61C>T) pathogenic?

CCZ1B p.Pro21Ser (c.61C>T) is classified Uncertain significance in CCZ1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely benign (0.0713); Absent from gnomAD v4.1.

How common is CCZ1B p.Pro21Ser (c.61C>T) in the general population?

CCZ1B p.Pro21Ser (c.61C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCZ1B p.Pro21Ser (c.61C>T)?

AlphaMissense predicts likely benign (score 0.0713) — an in-silico prediction, not a clinical call.

CCZ1B p.Pro21Ser

c.61C>T · VCV4650362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0713 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 851,240)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0713	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -8.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	phastCons 1
Regional constraint	o/e 0.23	constrained · MANE · 1,715 bp · p 2.7e-13 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 851,240). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCZ1B
Protein: p.Pro21Ser
Coding: c.61C>T
MANE Select: NM_198097
Type: single nucleotide variant
Location: chr7:6826137 (GRCh38)
Gene constraint: LOEUF 1.13 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.86 · 1 PDB

Full CCZ1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCZ1B p.Pro21Gln Uncertain significance ★ ⚠ same residue
CCZ1B p.Ala14Pro Uncertain significance ★ ⚠ same type
CCZ1B p.Ala155Gly Uncertain significance ★ ⚠ same type
CCZ1B p.Ala294Thr Uncertain significance ★ ⚠ same type
CCZ1B p.Ala323Asp Uncertain significance ★ ⚠ same type
CCZ1B p.Ala323Thr Conflicting classifications of pathogenicity ★ ⚠ same type
CCZ1B p.Ala330Gly Uncertain significance ★ ⚠ same type
CCZ1B p.Ala4Thr 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/ccz1b-p-pro21ser (accessed [today's date]).

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