Is CPAP p.Thr247Ala (c.739A>G) pathogenic?

CPAP p.Thr247Ala (c.739A>G) is classified Uncertain significance in CPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.0664); Very rare (popmax 0.00119%, nfe); Associated with Seckel syndrome 4.

What condition is associated with CPAP p.Thr247Ala (c.739A>G)?

CPAP p.Thr247Ala (c.739A>G) is associated with Seckel syndrome 4, microcephaly 6, primary, autosomal recessive (ClinVar).

How common is CPAP p.Thr247Ala (c.739A>G) in the general population?

CPAP p.Thr247Ala (c.739A>G) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about CPAP p.Thr247Ala (c.739A>G)?

AlphaMissense predicts likely benign (score 0.0664) — an in-silico prediction, not a clinical call.

CPAP p.Thr247Ala

c.739A>G · rs770285570 · VCV311626

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0664 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Seckel syndrome 4

Computational evidence

Protein change
AlphaMissense	0.0664	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -6.58	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 0.24	GERP -1.1
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	2.128	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,179,998 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000958% 14/1,461,874 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.Thr247Ala
Coding: c.739A>G
MANE Select: NM_018451
dbSNP: rs770285570
Type: single nucleotide variant
Location: chr13:24909916 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB

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

Disease context

Seckel syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microcephaly 6, primary, autosomal recessive

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-thr247ala (accessed [today's date]).

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