Is CWC27 p.Gln7Pro (c.20A>C) pathogenic?

CWC27 p.Gln7Pro (c.20A>C) is classified Uncertain significance in CWC27 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-03). AlphaMissense: likely pathogenic (0.9513); Ultra-rare (popmax 0.0427%, afr); Associated with Inborn genetic diseases.

What condition is associated with CWC27 p.Gln7Pro (c.20A>C)?

CWC27 p.Gln7Pro (c.20A>C) is associated with Inborn genetic diseases (ClinVar).

How common is CWC27 p.Gln7Pro (c.20A>C) in the general population?

CWC27 p.Gln7Pro (c.20A>C) is ultra-rare (popmax 0.0427%, afr) (gnomAD).

What do computational predictors say about CWC27 p.Gln7Pro (c.20A>C)?

AlphaMissense predicts likely pathogenic (score 0.9513) — an in-silico prediction, not a clinical call.

CWC27 p.Gln7Pro

c.20A>C · rs138792608 · VCV1056737

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9513 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0427%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9513	likely pathogenic
REVEL	0.373	indeterminate
SaProt	LLR -12.78	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 5.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 249 kb · p 0.12 · regional, not allelic
Overall
CADD	29.4	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

Grpmax group 0.0427% African / African-American · 32/74,912 alleles

Filtering AF 0.031% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0271%

Overall 0.00211% 34/1,614,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0427%	2,341
Admixed American	0.00167%	60,012
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Gln7Pro
Coding: c.20A>C
MANE Select: NM_005869
dbSNP: rs138792608
Type: single nucleotide variant
Location: chr5:64769166 (GRCh38)
Gene constraint: LOEUF 1.181 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.93 · 9 PDB
Residue 7: a UniProt-annotated variant site (in rpska)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CWC27 p.Gln7Arg Uncertain significance ★ same residue
CWC27 c.1042+5G>A Uncertain significance ★★ same condition
CWC27 p.Ala102Thr Uncertain significance ★★ ⚠ same condition
CWC27 p.Ala267Thr Uncertain significance ★★ ⚠ same condition
CWC27 p.Arg119Gln Uncertain significance ★★ ⚠ same condition
CWC27 p.Arg282Thr Uncertain significance ★★ ⚠ same condition
CWC27 p.Arg325Gln Uncertain significance ★★ ⚠ same condition
CWC27 p.Arg325Trp Uncertain significance ★★ ⚠ same condition

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-gln7pro (accessed [today's date]).

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