Is CPAP p.Gln347Pro (c.1040A>C) pathogenic?

CPAP p.Gln347Pro (c.1040A>C) is classified Uncertain significance in CPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: ambiguous (0.4527); Very rare (popmax 0.00333%, amr).

How common is CPAP p.Gln347Pro (c.1040A>C) in the general population?

CPAP p.Gln347Pro (c.1040A>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CPAP p.Gln347Pro (c.1040A>C)?

AlphaMissense predicts ambiguous (score 0.4527) — an in-silico prediction, not a clinical call.

CPAP p.Gln347Pro

c.1040A>C · rs754304759 · VCV2092525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4527 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4527	ambiguous
REVEL	0.077	moderately benign-leaning
SaProt	LLR -13.04	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.7	GERP -3
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	5.184	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,006 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00279% 45/1,613,862 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00626%	15,981
Admixed Americangrpmax	0.00333%	30,003
European (non-Finnish)	0.00322%	31,052
Remaining individualsnot grpmax-eligible	0.0016%	62,476

Finnish 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.Gln347Pro
Coding: c.1040A>C
MANE Select: NM_018451
dbSNP: rs754304759
Type: single nucleotide variant
Location: chr13:24907128 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 347: the 'alpha/beta-tubulin binding' region; an α-helix

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

Similar variants

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CPAP p.Arg378Ter Pathogenic ★★ same type
CPAP p.Arg566Ter Pathogenic/Likely pathogenic ★★ same type
CPAP p.Arg902Ter Pathogenic/Likely pathogenic ★★ same type
CPAP p.Arg958Ter Pathogenic/Likely pathogenic ★★ same type
CPAP p.Gln14Ter Pathogenic/Likely pathogenic ★★ same type
CPAP p.Gln657Ter Pathogenic/Likely pathogenic ★★ 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-gln347pro (accessed [today's date]).

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