Is CWC27 c.252+1G>A pathogenic?

CWC27 c.252+1G>A is classified Likely pathogenic in CWC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-11). Very rare (popmax 0.00145%, afr).

How common is CWC27 c.252+1G>A in the general population?

CWC27 c.252+1G>A is very rare (popmax 0.00145%, afr) (gnomAD).

CWC27 c.252+1G>A

rs1468432566 · VCV2963690

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00145%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	Δ0.92	donor loss · deltas
Pangolin	Δ0.85	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 5.6, phastCons 1
Non-coding constraint	Z 2.19	1 kb window · o/e 0.80 · regional · uncalibrated
Overall
CADD	33.0	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 0.00145% African / African-American · 1/68,846 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.3e-05%

Overall 0.000293% 4/1,367,260 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00145%	68,846
European (non-Finnish)	0.000304%	328,539

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
Coding: c.252+1G>A
MANE Select: NM_005869
dbSNP: rs1468432566
Type: single nucleotide variant
Location: chr5:64782034 (GRCh38)
Gene constraint: LOEUF 1.181 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.93 · 9 PDB

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-c-252-plus-1g-a (accessed [today's date]).

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