Is CPAP p.Arg566Ter (c.1696C>T) pathogenic?

CPAP p.Arg566Ter (c.1696C>T) is classified Pathogenic/Likely pathogenic in CPAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-24). Very rare (popmax 0.00348%, nfe); Associated with microcephaly 6, primary, autosomal recessive.

What condition is associated with CPAP p.Arg566Ter (c.1696C>T)?

CPAP p.Arg566Ter (c.1696C>T) is associated with microcephaly 6, primary, autosomal recessive (ClinVar).

How common is CPAP p.Arg566Ter (c.1696C>T) in the general population?

CPAP p.Arg566Ter (c.1696C>T) is very rare (popmax 0.00348%, nfe) (gnomAD).

CPAP p.Arg566Ter

c.1696C>T · rs138228629 · VCV280184

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00348%, 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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.82, phastCons 1
Overall
CADD	36.0	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 0.00348% European (non-Finnish) · 41/1,179,558 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.00285% 46/1,611,786 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00348%	28,770
African / African-American	0.00268%	37,287
Admixed American	0.00168%	59,402
Finnishnot grpmax-eligible	0.00156%	63,982
South Asian	0.0011%	90,512

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.Arg566Ter
Coding: c.1696C>T
MANE Select: NM_018451
dbSNP: rs138228629
Type: single nucleotide variant
Location: chr13:24906342 (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.Arg1298Gln Likely pathogenic ★★ same condition
CPAP p.Arg378Ter Pathogenic ★★ same condition
CPAP p.Arg958Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Gln14Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Gln657Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Glu212Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Glu955Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Ser529Ter 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-arg566ter (accessed [today's date]).

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