Is CPAP p.Ala925Ser (c.2773G>T) pathogenic?

CPAP p.Ala925Ser (c.2773G>T) is classified Uncertain significance in CPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-10). AlphaMissense: likely benign (0.0937); Very rare (popmax 0.004%, afr).

How common is CPAP p.Ala925Ser (c.2773G>T) in the general population?

CPAP p.Ala925Ser (c.2773G>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CPAP p.Ala925Ser (c.2773G>T)?

AlphaMissense predicts likely benign (score 0.0937) — an in-silico prediction, not a clinical call.

CPAP p.Ala925Ser

c.2773G>T · rs371350350 · VCV1934698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0937 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0937	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -5.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -2.2, phastCons 0.011
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	13.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,932 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,758 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,977
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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.Ala925Ser
Coding: c.2773G>T
MANE Select: NM_018451
dbSNP: rs371350350
Type: single nucleotide variant
Location: chr13:24903978 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 925: the 'interaction with stil' region

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

Similar variants

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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-ala925ser (accessed [today's date]).

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