Is CPAP p.Thr255Ala (c.763A>G) pathogenic?

CPAP p.Thr255Ala (c.763A>G) is classified Benign/Likely benign in CPAP (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0739); Low-frequency (popmax 2.06%, eas); Associated with microcephaly 6, primary, autosomal recessive.

What condition is associated with CPAP p.Thr255Ala (c.763A>G)?

CPAP p.Thr255Ala (c.763A>G) is associated with microcephaly 6, primary, autosomal recessive, Seckel syndrome 4 (ClinVar).

How common is CPAP p.Thr255Ala (c.763A>G) in the general population?

CPAP p.Thr255Ala (c.763A>G) is low-frequency (popmax 2.06%, eas) (gnomAD).

What do computational predictors say about CPAP p.Thr255Ala (c.763A>G)?

AlphaMissense predicts likely benign (score 0.0739) — an in-silico prediction, not a clinical call.

CPAP p.Thr255Ala

c.763A>G · rs150932292 · VCV499422

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0739 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.06%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly 6, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.0739	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -6.52	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 -0.34	GERP -2.8
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	8.712	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 2.06% East Asian · 923/44,882 alleles

Filtering AF 1.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9%

Overall 0.0646% 1,043/1,614,130 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.06%	49
Remaining individualsnot grpmax-eligible	0.08%	1,250
South Asian	0.0461%	2,168
Admixed American	0.00666%	15,007
European (non-Finnish)	0.00195%	51,305
Finnishnot grpmax-eligible	0.00156%	64,034

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.Thr255Ala
Coding: c.763A>G
MANE Select: NM_018451
dbSNP: rs150932292
Type: single nucleotide variant
Location: chr13:24909892 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB

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-thr255ala (accessed [today's date]).

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