Is CPAP p.Ala259Val (c.776C>T) pathogenic?

CPAP p.Ala259Val (c.776C>T) is classified Benign/Likely benign in CPAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-22). AlphaMissense: likely benign (0.0908); Rare (popmax 0.148%, sas).

How common is CPAP p.Ala259Val (c.776C>T) in the general population?

CPAP p.Ala259Val (c.776C>T) is rare (popmax 0.148%, sas) (gnomAD).

What do computational predictors say about CPAP p.Ala259Val (c.776C>T)?

AlphaMissense predicts likely benign (score 0.0908) — an in-silico prediction, not a clinical call.

CPAP p.Ala259Val

c.776C>T · rs532917061 · VCV1620822

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0908 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0908	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -6.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP -0.72, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	17.61	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 0.148% South Asian · 135/91,042 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.12%

Overall 0.0123% 199/1,613,652 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.148%	674
East Asian	0.00891%	11,222
Remaining individualsnot grpmax-eligible	0.0048%	20,831
European (non-Finnish)	0.00458%	21,846
Admixed American	0.00333%	29,998
African / African-American	0.00133%	74,980

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.Ala259Val
Coding: c.776C>T
MANE Select: NM_018451
dbSNP: rs532917061
Type: single nucleotide variant
Location: chr13:24909879 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB

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

Similar variants

CPAP p.Ala259= Likely benign ★★ same residue
CPAP p.Ala259_Ser260insTer Likely benign same residue
CPAP c.2693-2A>G Likely pathogenic ★★ same type
CPAP p.Arg1298Gln Likely pathogenic ★★ same type
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

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-ala259val (accessed [today's date]).

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