Is CPAP p.Gln1027Arg (c.3080A>G) pathogenic?

CPAP p.Gln1027Arg (c.3080A>G) is classified Uncertain significance in CPAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-01-15). AlphaMissense: ambiguous (0.3738); Ultra-rare (popmax 0.0774%, afr); Associated with microcephaly 6, primary, autosomal recessive.

What condition is associated with CPAP p.Gln1027Arg (c.3080A>G)?

CPAP p.Gln1027Arg (c.3080A>G) is associated with microcephaly 6, primary, autosomal recessive, Seckel syndrome 4 (ClinVar).

How common is CPAP p.Gln1027Arg (c.3080A>G) in the general population?

CPAP p.Gln1027Arg (c.3080A>G) is ultra-rare (popmax 0.0774%, afr) (gnomAD).

What do computational predictors say about CPAP p.Gln1027Arg (c.3080A>G)?

AlphaMissense predicts ambiguous (score 0.3738) — an in-silico prediction, not a clinical call.

CPAP p.Gln1027Arg

c.3080A>G · rs141237492 · VCV1395151

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3738 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0774%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

microcephaly 6, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.3738	ambiguous
REVEL	0.171	moderately benign-leaning
SaProt	LLR -8.68	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	24.7	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 0.0774% African / African-American · 58/74,908 alleles

Filtering AF 0.0614% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0557%

Overall 0.00415% 67/1,613,870 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0774%	1,292
Admixed American	0.0117%	8,569
Remaining individualsnot grpmax-eligible	0.0032%	31,240

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.Gln1027Arg
Coding: c.3080A>G
MANE Select: NM_018451
dbSNP: rs141237492
Type: single nucleotide variant
Location: chr13:24892779 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 1027: the 'interaction with stil' region

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.Gln1027His Uncertain significance ★★ ⚠ same residue
CPAP p.Gln1027Ter Likely pathogenic ★ same residue
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

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-gln1027arg (accessed [today's date]).

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