Is CWC27 p.Phe202fs (c.606del) pathogenic?

CWC27 p.Phe202fs (c.606del) is classified Pathogenic in CWC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-08). Very rare (popmax 0.00138%, nfe).

How common is CWC27 p.Phe202fs (c.606del) in the general population?

CWC27 p.Phe202fs (c.606del) is very rare (popmax 0.00138%, nfe) (gnomAD).

CWC27 p.Phe202fs

c.606del · rs777801764 · VCV1419612

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00138%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00138% European (non-Finnish) · 16/1,163,164 alleles

Filtering AF 0.000814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000659%

Overall 0.00102% 16/1,576,256 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: CWC27
Protein: p.Phe202fs
Coding: c.606del
MANE Select: NM_005869
dbSNP: rs777801764
Type: Deletion
Location: chr5:64788954 (GRCh38)
Gene constraint: LOEUF 1.181 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.93 · 9 PDB
Residue 202: a UniProt-annotated variant site (in rpska)

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

Similar variants

CWC27 c.249_252+22del Likely pathogenic ★★ same type
CWC27 p.Ala356fs Pathogenic ★★ same type
CWC27 p.Asn109fs Pathogenic/Likely pathogenic ★★ same type
CWC27 p.Gly253fs Pathogenic/Likely pathogenic ★★ same type
CWC27 p.Lys334_Val335insTer Pathogenic/Likely pathogenic ★★ same type
CWC27 p.Ser222fs Pathogenic ★★ same type
CWC27 p.Glu470fs Uncertain significance ★★ same type
CWC27 c.1257-7del Likely benign ★★ 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-phe202fs (accessed [today's date]).

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