Is CPAP p.Ser469fs (c.1404_1407del) pathogenic?

CPAP p.Ser469fs (c.14041407del) is classified Pathogenic in CPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2015-07-22). Very rare (popmax 8.47e-05%, nfe); Associated with Seckel syndrome 4.

What condition is associated with CPAP p.Ser469fs (c.1404_1407del)?

CPAP p.Ser469fs (c.1404_1407del) is associated with Seckel syndrome 4 (ClinVar).

How common is CPAP p.Ser469fs (c.1404_1407del) in the general population?

CPAP p.Ser469fs (c.1404_1407del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CPAP p.Ser469fs

c.1404_1407del · rs777893196 · VCV210657

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Seckel syndrome 4

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 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP 0.67, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.84e-05% 1/1,461,870 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: CPAP
Protein: p.Ser469fs
Coding: c.1404_1407del
MANE Select: NM_018451
dbSNP: rs777893196
Type: Deletion
Location: chr13:24906631 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 469: the 'disordered' region

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

Disease context

Seckel syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPAP p.Glu300fs Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Lys479fs Pathogenic ★★ same condition
CPAP p.Ala628fs Pathogenic ★ same condition
CPAP p.Gly1086_Thr1087del Likely pathogenic ★ same condition
CPAP p.Pro617fs Pathogenic ★ same condition
CPAP p.Ser469Phe Uncertain significance ★ ⚠ same residue
CPAP p.Arg958Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Gln14Ter Pathogenic/Likely pathogenic ★★ 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/cpap-p-ser469fs (accessed [today's date]).

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