Is CPAP p.Pro1221= (c.3663G>A) pathogenic?

CPAP p.Pro1221= (c.3663G>A) is classified Conflicting classifications of pathogenicity in CPAP (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0258%, nfe).

How common is CPAP p.Pro1221= (c.3663G>A) in the general population?

CPAP p.Pro1221= (c.3663G>A) is ultra-rare (popmax 0.0258%, nfe) (gnomAD).

CPAP p.Pro1221=

c.3663G>A · rs200291056 · VCV286071

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0258%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -7.2	GERP -3.7
Overall
CADD	0.165	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0258% European (non-Finnish) · 305/1,180,004 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0225%

Overall 0.0201% 324/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0258%	3,869
Remaining individualsnot grpmax-eligible	0.0192%	5,207
African / African-American	0.00668%	14,981
South Asian	0.0022%	45,545

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.Pro1221=
Coding: c.3663G>A
MANE Select: NM_031277 · reported on NM_018451
dbSNP: rs200291056
Type: single nucleotide variant
Location: chr13:24884201 (GRCh38)

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

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-pro1221 (accessed [today's date]).

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