Is CPAP p.Trp1053Cys (c.3159G>T) pathogenic?

CPAP p.Trp1053Cys (c.3159G>T) is classified Uncertain significance in CPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely pathogenic (0.9067); Very rare (popmax 0.00127%, nfe); Associated with microcephaly 6, primary, autosomal recessive.

What condition is associated with CPAP p.Trp1053Cys (c.3159G>T)?

CPAP p.Trp1053Cys (c.3159G>T) is associated with microcephaly 6, primary, autosomal recessive, Seckel syndrome 4 (ClinVar).

How common is CPAP p.Trp1053Cys (c.3159G>T) in the general population?

CPAP p.Trp1053Cys (c.3159G>T) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about CPAP p.Trp1053Cys (c.3159G>T)?

AlphaMissense predicts likely pathogenic (score 0.9067) — an in-silico prediction, not a clinical call.

CPAP p.Trp1053Cys

c.3159G>T · rs751422006 · VCV881664

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9067 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly 6, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.9067	likely pathogenic · top 3% in CPAP
REVEL	0.212	benign-leaning
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	25.3	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 0.00127% European (non-Finnish) · 15/1,180,026 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000929% 15/1,614,026 alleles · very rare

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.Trp1053Cys
Coding: c.3159G>T
MANE Select: NM_018451
dbSNP: rs751422006
Type: single nucleotide variant
Location: chr13:24892700 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 1053: 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.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-trp1053cys (accessed [today's date]).

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