Is CWC27 p.Ser311Arg (c.933C>G) pathogenic?

CWC27 p.Ser311Arg (c.933C>G) is classified Uncertain significance in CWC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). AlphaMissense: likely pathogenic (0.7897); Absent from gnomAD v4.1.

How common is CWC27 p.Ser311Arg (c.933C>G) in the general population?

CWC27 p.Ser311Arg (c.933C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CWC27 p.Ser311Arg (c.933C>G)?

AlphaMissense predicts likely pathogenic (score 0.7897) — an in-silico prediction, not a clinical call.

CWC27 p.Ser311Arg

c.933C>G · rs2112214950 · VCV1394526

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7897 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7897	likely pathogenic
REVEL	0.074	moderately benign-leaning
SaProt	LLR -7.74	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -1.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 249 kb · p 0.12 · regional, not allelic
Overall
CADD	16.83	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

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: CWC27
Protein: p.Ser311Arg
Coding: c.933C>G
MANE Select: NM_005869
dbSNP: rs2112214950
Type: single nucleotide variant
Location: chr5:64804381 (GRCh38)
Gene constraint: LOEUF 1.181 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.93 · 9 PDB
Residue 311: a UniProt-annotated variant site (in rpska); the 'disordered' region

Full CWC27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CWC27 c.1152+2T>A Likely pathogenic ★★ same type
CWC27 c.397-1G>A Likely pathogenic ★★ same type
CWC27 c.938+2T>C Likely pathogenic ★★ same type
CWC27 p.Arg143Ter Pathogenic/Likely pathogenic ★★ same type
CWC27 p.Gln374Ter Pathogenic/Likely pathogenic ★★ same type
CWC27 p.Glu165= Pathogenic ★★ same type
CWC27 p.Tyr367Ter Pathogenic/Likely pathogenic ★★ same type
CWC27 c.1042+5G>A 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/cwc27-p-ser311arg (accessed [today's date]).

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