Is CPAP p.Asp63His (c.187G>C) pathogenic?

CPAP p.Asp63His (c.187G>C) is classified Benign/Likely benign in CPAP (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1156); Common (popmax 7.31%, afr) — too common for a highly-penetrant pathogenic allele; Associated with microcephaly 6, primary, autosomal recessive.

What condition is associated with CPAP p.Asp63His (c.187G>C)?

CPAP p.Asp63His (c.187G>C) is associated with microcephaly 6, primary, autosomal recessive, Seckel syndrome 4 (ClinVar).

What do computational predictors say about CPAP p.Asp63His (c.187G>C)?

AlphaMissense predicts likely benign (score 0.1156) — an in-silico prediction, not a clinical call.

CPAP p.Asp63His

Q: How common is CPAP p.Asp63His (c.187G>C) in the general population?

CPAP p.Asp63His (c.187G>C) is common (popmax 7.31%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.187G>C · rs7336216 · VCV21660

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.1156 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.31%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly 6, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.1156	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.28	GERP -1.1, phastCons 0.46
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	18.25	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 7.31% African / African-American · 5,483/75,014 alleles

Filtering AF 7.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.08%

Overall 0.391% 6,313/1,614,124 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.31%	14
Remaining individualsnot grpmax-eligible	0.538%	186
Admixed American	0.515%	194
Middle Eastern	0.478%	209
South Asian	0.0307%	3,253
European (non-Finnish)	0.0108%	9,219

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.Asp63His
Coding: c.187G>C
MANE Select: NM_018451
dbSNP: rs7336216
Type: single nucleotide variant
Location: chr13:24912839 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 63: a UniProt-annotated variant site (in)

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

Disease context

microcephaly 6, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 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-asp63his (accessed [today's date]).

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