Is CPAP p.Gln1027His (c.3081G>T) pathogenic?

CPAP p.Gln1027His (c.3081G>T) is classified Uncertain significance in CPAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2020-11-30). AlphaMissense: likely pathogenic (0.7744); Absent from gnomAD v4.1; Associated with microcephaly 6, primary, autosomal recessive.

What condition is associated with CPAP p.Gln1027His (c.3081G>T)?

CPAP p.Gln1027His (c.3081G>T) is associated with microcephaly 6, primary, autosomal recessive (ClinVar).

How common is CPAP p.Gln1027His (c.3081G>T) in the general population?

CPAP p.Gln1027His (c.3081G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPAP p.Gln1027His (c.3081G>T)?

AlphaMissense predicts likely pathogenic (score 0.7744) — an in-silico prediction, not a clinical call.

CPAP p.Gln1027His

c.3081G>T · rs1593540180 · VCV806995

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

microcephaly 6, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.7744	likely pathogenic · top 7% in CPAP
REVEL	0.367	indeterminate
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.94	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	22.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPAP
Protein: p.Gln1027His
Coding: c.3081G>T
MANE Select: NM_018451
dbSNP: rs1593540180
Type: single nucleotide variant
Location: chr13:24892778 (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

Similar variants

CPAP p.Gln1027Arg 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-gln1027his (accessed [today's date]).

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