Is CPAP p.Gln200His (c.600G>T) pathogenic?

CPAP p.Gln200His (c.600G>T) is classified Conflicting classifications of pathogenicity in CPAP (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-14). AlphaMissense: likely benign (0.1842); Rare (popmax 0.15%, amr); Associated with Inborn genetic diseases.

What condition is associated with CPAP p.Gln200His (c.600G>T)?

CPAP p.Gln200His (c.600G>T) is associated with Inborn genetic diseases, microcephaly 6, primary, autosomal recessive, Seckel syndrome 4 (ClinVar).

How common is CPAP p.Gln200His (c.600G>T) in the general population?

CPAP p.Gln200His (c.600G>T) is rare (popmax 0.15%, amr) (gnomAD).

What do computational predictors say about CPAP p.Gln200His (c.600G>T)?

AlphaMissense predicts likely benign (score 0.1842) — an in-silico prediction, not a clinical call.

CPAP p.Gln200His

c.600G>T · rs200061825 · VCV158216

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1842 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.15%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1842	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -6.82	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 0.79	GERP -1.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	18.64	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 0.15% Admixed American · 90/60,016 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.00682% 110/1,613,404 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.15%	667
Remaining individualsnot grpmax-eligible	0.0272%	3,673
African / African-American	0.00267%	37,511
European (non-Finnish)	8.47e-05%	1,179,998

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.Gln200His
Coding: c.600G>T
MANE Select: NM_018451
dbSNP: rs200061825
Type: single nucleotide variant
Location: chr13:24910055 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 200: 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

Also linked: microcephaly 6, primary, autosomal recessive Seckel syndrome 4

Similar variants

CPAP p.Arg1298Gln Likely pathogenic ★★ same condition
CPAP p.Arg378Ter Pathogenic ★★ same condition
CPAP p.Arg566Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Arg958Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Gln14Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Gln657Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Glu212Ter Pathogenic/Likely pathogenic ★★ same condition
CPAP p.Glu955Ter Pathogenic/Likely pathogenic ★★ 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-gln200his (accessed [today's date]).

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