Is CPAP p.Pro627Leu (c.1880C>T) pathogenic?

CPAP p.Pro627Leu (c.1880C>T) is classified Uncertain significance in CPAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-31). AlphaMissense: likely benign (0.0663); Very rare (popmax 0.00517%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CPAP p.Pro627Leu (c.1880C>T)?

CPAP p.Pro627Leu (c.1880C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CPAP p.Pro627Leu (c.1880C>T) in the general population?

CPAP p.Pro627Leu (c.1880C>T) is very rare (popmax 0.00517%, nfe) (gnomAD).

What do computational predictors say about CPAP p.Pro627Leu (c.1880C>T)?

AlphaMissense predicts likely benign (score 0.0663) — an in-silico prediction, not a clinical call.

CPAP p.Pro627Leu

c.1880C>T · rs772020507 · VCV210659

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0663 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0663	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -5.89	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 0.64	GERP -3.7
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	1.842	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 0.00517% European (non-Finnish) · 61/1,179,724 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00421% 68/1,613,566 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,340
Admixed American	0.005%	19,989
South Asian	0.0022%	45,515
Remaining individualsnot grpmax-eligible	0.0016%	62,466
African / African-American	0.00134%	74,890

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.Pro627Leu
Coding: c.1880C>T
MANE Select: NM_018451
dbSNP: rs772020507
Type: single nucleotide variant
Location: chr13:24906158 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 627: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPAP p.Pro627= Benign ★★ same residue
CPAP p.Ala137Ser Uncertain significance ★★ ⚠ same condition
CPAP p.Arg535Trp Uncertain significance ★★ ⚠ same condition
CPAP p.Arg692His Uncertain significance ★★ ⚠ same condition
CPAP p.Arg723Gly Uncertain significance ★★ ⚠ same condition
CPAP p.Asn1175Ser Uncertain significance ★★ ⚠ same condition
CPAP p.Asp730His Uncertain significance ★★ ⚠ same condition
CPAP p.Asp743Gly Uncertain significance ★★ ⚠ same condition

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-pro627leu (accessed [today's date]).

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