Is CPAP p.Arg692His (c.2075G>A) pathogenic?

CPAP p.Arg692His (c.2075G>A) is classified Uncertain significance in CPAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-16). AlphaMissense: likely benign (0.0865); Ultra-rare (popmax 0.0439%, sas); Associated with Inborn genetic diseases.

What condition is associated with CPAP p.Arg692His (c.2075G>A)?

CPAP p.Arg692His (c.2075G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CPAP p.Arg692His (c.2075G>A) in the general population?

CPAP p.Arg692His (c.2075G>A) is ultra-rare (popmax 0.0439%, sas) (gnomAD).

What do computational predictors say about CPAP p.Arg692His (c.2075G>A)?

AlphaMissense predicts likely benign (score 0.0865) — an in-silico prediction, not a clinical call.

CPAP p.Arg692His

c.2075G>A · rs200890637 · VCV1385664

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0865 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0865	likely benign
REVEL	0.135	moderately 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 0.49	GERP 1.9
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	13.35	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 0.0439% South Asian · 40/91,094 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00397% 64/1,614,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0439%	2,277
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Admixed American	0.00167%	60,002
Finnishnot grpmax-eligible	0.00156%	64,024
European (non-Finnish)	0.00144%	69,414
African / African-American	0.00134%	74,902

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.Arg692His
Coding: c.2075G>A
MANE Select: NM_018451
dbSNP: rs200890637
Type: single nucleotide variant
Location: chr13:24905963 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 692: 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.Arg692Cys Uncertain significance ★ ⚠ same residue
CPAP p.Ala137Ser Uncertain significance ★★ ⚠ same condition
CPAP p.Arg535Trp 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
CPAP p.Asp762Glu 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-arg692his (accessed [today's date]).

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