Is CWC25 p.Ser210Pro (c.628T>C) pathogenic?

CWC25 p.Ser210Pro (c.628T>C) is classified Uncertain significance in CWC25 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.0798); Absent from gnomAD v4.1.

How common is CWC25 p.Ser210Pro (c.628T>C) in the general population?

CWC25 p.Ser210Pro (c.628T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CWC25 p.Ser210Pro (c.628T>C)?

AlphaMissense predicts likely benign (score 0.0798) — an in-silico prediction, not a clinical call.

CWC25 p.Ser210Pro

c.628T>C · VCV4657760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0798 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0798	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -7.15	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 7.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 19 kb · p 0.014 · regional, not allelic
Overall
CADD	20.7	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

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: CWC25
Protein: p.Ser210Pro
Coding: c.628T>C
MANE Select: NM_017748
Type: single nucleotide variant
Location: chr17:38809764 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.55 · 4 PDB
Residue 210: the 'disordered' region

Full CWC25 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CWC25 p.Ala124Gly Uncertain significance ★ ⚠ same type
CWC25 p.Ala329Val Uncertain significance ★ ⚠ same type
CWC25 p.Ala367Ser Uncertain significance ★ ⚠ same type
CWC25 p.Ala367Thr Uncertain significance ★ ⚠ same type
CWC25 p.Arg135Gln Uncertain significance ★ ⚠ same type
CWC25 p.Arg135Trp Uncertain significance ★ ⚠ same type
CWC25 p.Arg151Gln Uncertain significance ★ ⚠ same type
CWC25 p.Arg198Cys 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/cwc25-p-ser210pro (accessed [today's date]).

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