Is CWC25 p.Ser201Arg (c.603C>G) pathogenic?

CWC25 p.Ser201Arg (c.603C>G) is classified Uncertain significance in CWC25 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-20). AlphaMissense: likely benign (0.2549); Very rare (popmax 0.00017%, nfe).

How common is CWC25 p.Ser201Arg (c.603C>G) in the general population?

CWC25 p.Ser201Arg (c.603C>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CWC25 p.Ser201Arg (c.603C>G)?

AlphaMissense predicts likely benign (score 0.2549) — an in-silico prediction, not a clinical call.

CWC25 p.Ser201Arg

c.603C>G · rs2508929638 · VCV2609014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2549 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2549	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -11.31	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -4
Regional constraint	o/e 0.89	unconstrained · MANE · 19 kb · p 0.014 · regional, not allelic
Overall
CADD	5.899	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,174,292 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000138% 2/1,449,670 alleles · very rare

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: CWC25
Protein: p.Ser201Arg
Coding: c.603C>G
MANE Select: NM_017748
dbSNP: rs2508929638
Type: single nucleotide variant
Location: chr17:38810491 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.55 · 4 PDB
Residue 201: 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-ser201arg (accessed [today's date]).

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