Is CPAP p.Lys42fs (c.125_126del) pathogenic?

CPAP p.Lys42fs (c.125126del) is classified Pathogenic in CPAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-25). Ultra-rare (popmax 0.033%, mid).

How common is CPAP p.Lys42fs (c.125_126del) in the general population?

CPAP p.Lys42fs (c.125_126del) is ultra-rare (popmax 0.033%, mid) (gnomAD).

CPAP p.Lys42fs

c.125_126del · rs1441504335 · VCV1453667

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 2 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000274% 4/1,461,878 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	8.47e-05%	1,180,022

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: CPAP
Protein: p.Lys42fs
Coding: c.125_126del
MANE Select: NM_018451
dbSNP: rs1441504335
Type: Deletion
Location: chr13:24912900 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB

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

Similar variants

CPAP p.Gln169fs Pathogenic/Likely pathogenic ★★ same type
CPAP p.Gln311fs Pathogenic ★★ same type
CPAP p.Glu300fs Pathogenic/Likely pathogenic ★★ same type
CPAP p.Glu344fs Pathogenic/Likely pathogenic ★★ same type
CPAP p.Lys479fs Pathogenic ★★ same type
CPAP p.Ser1081fs Pathogenic/Likely pathogenic ★★ same type
CPAP p.Ser7fs Pathogenic ★★ same type
CPAP c.2992-18_2992-16del 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/cpap-p-lys42fs (accessed [today's date]).

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