Is CPAP p.Arg645Cys (c.1933C>T) pathogenic?

CPAP p.Arg645Cys (c.1933C>T) is classified Likely benign in CPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). AlphaMissense: likely benign (0.0823); Very rare (popmax 0.00834%, amr); Associated with Inborn genetic diseases.

What condition is associated with CPAP p.Arg645Cys (c.1933C>T)?

CPAP p.Arg645Cys (c.1933C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CPAP p.Arg645Cys (c.1933C>T) in the general population?

CPAP p.Arg645Cys (c.1933C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about CPAP p.Arg645Cys (c.1933C>T)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

CPAP p.Arg645Cys

c.1933C>T · rs541232925 · VCV2349094

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -6.87	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 -1.3	GERP -3.4
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	0.605	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 0.00834% Admixed American · 5/59,960 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00105% 17/1,612,656 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,992
African / African-American	0.00267%	37,480
East Asian	0.00223%	44,854
European (non-Finnish)	0.000763%	131,012

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.Arg645Cys
Coding: c.1933C>T
MANE Select: NM_018451
dbSNP: rs541232925
Type: single nucleotide variant
Location: chr13:24906105 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 645: 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.Arg645His Uncertain significance ★ ⚠ 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-arg645cys (accessed [today's date]).

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