Is CPAP p.Ala130Val (c.389C>T) pathogenic?

CPAP p.Ala130Val (c.389C>T) is classified Uncertain significance in CPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely benign (0.0886); Very rare (popmax 0.0033%, sas).

How common is CPAP p.Ala130Val (c.389C>T) in the general population?

CPAP p.Ala130Val (c.389C>T) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about CPAP p.Ala130Val (c.389C>T)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

CPAP p.Ala130Val

c.389C>T · rs190803157 · VCV420931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.90	donor gain · deltas
Pangolin	Δ0.75	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1.5	GERP -3.7
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	14.25	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 0.0033% South Asian · 3/90,874 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.0018% 29/1,613,448 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,291
Remaining individualsnot grpmax-eligible	0.0032%	31,238
African / African-American	0.00267%	37,404
East Asian	0.00223%	44,896
European (non-Finnish)	0.0017%	58,996
Admixed American	0.00167%	59,878

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.Ala130Val
Coding: c.389C>T
MANE Select: NM_018451
dbSNP: rs190803157
Type: single nucleotide variant
Location: chr13:24912637 (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.Ala130= 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
CPAP p.Gln14Ter 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-ala130val (accessed [today's date]).

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