Is CWC27 p.Pro34Ser (c.100C>T) pathogenic?

CWC27 p.Pro34Ser (c.100C>T) is classified Uncertain significance in CWC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: likely pathogenic (0.9702); Absent from gnomAD v4.1.

How common is CWC27 p.Pro34Ser (c.100C>T) in the general population?

CWC27 p.Pro34Ser (c.100C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CWC27 p.Pro34Ser (c.100C>T)?

AlphaMissense predicts likely pathogenic (score 0.9702) — an in-silico prediction, not a clinical call.

CWC27 p.Pro34Ser

c.100C>T · rs141974787 · VCV1360521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9702 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9702	likely pathogenic
REVEL	0.885	moderately pathogenic-leaning
SaProt	LLR -13.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 5.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 249 kb · p 0.12 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: CWC27
Protein: p.Pro34Ser
Coding: c.100C>T
MANE Select: NM_005869
dbSNP: rs141974787
Type: single nucleotide variant
Location: chr5:64774748 (GRCh38)
Gene constraint: LOEUF 1.181 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.93 · 9 PDB
Residue 34: the ppiase cyclophilin-type domain; a UniProt-annotated variant site (in rpska); an α-helix

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

Similar variants

CWC27 p.Pro34Thr Uncertain significance ★★ ⚠ same residue
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

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-pro34ser (accessed [today's date]).

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