Is CPAP p.Arg612Gln (c.1835G>A) pathogenic?

CPAP p.Arg612Gln (c.1835G>A) is classified Uncertain significance in CPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-04). AlphaMissense: likely benign (0.098); Very rare (popmax 0.00801%, afr); Associated with Inborn genetic diseases.

What condition is associated with CPAP p.Arg612Gln (c.1835G>A)?

CPAP p.Arg612Gln (c.1835G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CPAP p.Arg612Gln (c.1835G>A) in the general population?

CPAP p.Arg612Gln (c.1835G>A) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CPAP p.Arg612Gln (c.1835G>A)?

AlphaMissense predicts likely benign (score 0.098) — an in-silico prediction, not a clinical call.

CPAP p.Arg612Gln

c.1835G>A · VCV3265924

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.098 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.098	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -5.86	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 0.16, phastCons 0.003
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	20.8	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 0.00801% African / African-American · 6/74,894 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00167% 27/1,612,982 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,482
Admixed American	0.00501%	19,969
South Asian	0.0022%	45,492
Remaining individualsnot grpmax-eligible	0.0016%	62,410
Finnishnot grpmax-eligible	0.00156%	64,004
European (non-Finnish)	0.00119%	84,239

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.Arg612Gln
Coding: c.1835G>A
MANE Select: NM_018451
Type: single nucleotide variant
Location: chr13:24906203 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 612: 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.Arg612Trp Uncertain significance ★★ ⚠ same residue
CPAP p.Arg612= Likely 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

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-arg612gln (accessed [today's date]).

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