Is CPAP p.Gln169fs (c.505_506del) pathogenic?

CPAP p.Gln169fs (c.505506del) is classified Pathogenic/Likely pathogenic in CPAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-27). Very rare (popmax 0.00593%, nfe); Associated with microcephaly 6, primary, autosomal recessive.

What condition is associated with CPAP p.Gln169fs (c.505_506del)?

CPAP p.Gln169fs (c.505_506del) is associated with microcephaly 6, primary, autosomal recessive (ClinVar).

How common is CPAP p.Gln169fs (c.505_506del) in the general population?

CPAP p.Gln169fs (c.505_506del) is very rare (popmax 0.00593%, nfe) (gnomAD).

CPAP p.Gln169fs

c.505_506del · rs747993775 · VCV2429273

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00593%, nfe)

Conditions

microcephaly 6, primary, autosomal recessive

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 3 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1	GERP -3.7, phastCons 0.003
Overall
CADD	28.4	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 0.00593% European (non-Finnish) · 70/1,179,988 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.00483% 78/1,614,038 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0112%	8,927
European (non-Finnish)grpmax	0.00593%	16,857
African / African-American	0.00133%	74,928

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln169fs
Coding: c.505_506del
MANE Select: NM_018451
dbSNP: rs747993775
Type: Deletion
Location: chr13:24912008 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB

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

Disease context

microcephaly 6, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPAP p.Ser1081fs Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Ser7fs Pathogenic ★★ same condition
CPAP p.Leu1133fs Pathogenic ★ same condition
CPAP p.Arg1298Gln Likely pathogenic ★★ same condition
CPAP p.Arg378Ter Pathogenic ★★ same condition
CPAP p.Arg566Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Arg958Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Asp705_Ser706insTer 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-gln169fs (accessed [today's date]).

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