Is CPAP p.Pro55Ala (c.163C>G) pathogenic?

CPAP p.Pro55Ala (c.163C>G) is classified Benign/Likely benign in CPAP (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.0868); Common (popmax 8.69%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Seckel syndrome 4.

What condition is associated with CPAP p.Pro55Ala (c.163C>G)?

CPAP p.Pro55Ala (c.163C>G) is associated with Seckel syndrome 4, microcephaly 6, primary, autosomal recessive (ClinVar).

What do computational predictors say about CPAP p.Pro55Ala (c.163C>G)?

AlphaMissense predicts likely benign (score 0.0868) — an in-silico prediction, not a clinical call.

CPAP p.Pro55Ala

Q: How common is CPAP p.Pro55Ala (c.163C>G) in the general population?

CPAP p.Pro55Ala (c.163C>G) is common (popmax 8.69%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.163C>G · rs17081389 · VCV21659

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0868 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.69%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Seckel syndrome 4

Computational evidence

Protein change
AlphaMissense	0.0868	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -6.98	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 3.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	13.19	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 8.69% African / African-American · 6,518/74,998 alleles

Filtering AF 8.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.44%

Overall 0.488% 7,874/1,614,104 alleles · common exomes 4,178/1,461,872 · genomes 3,696/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.69%	12
Middle Eastern	1.44%	70
Remaining individualsnot grpmax-eligible	0.653%	153
Admixed American	0.573%	174
European (non-Finnish)	0.0418%	2,394
South Asian	0.0231%	4,337
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,867

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.Pro55Ala
Coding: c.163C>G
MANE Select: NM_018451
dbSNP: rs17081389
Type: single nucleotide variant
Location: chr13:24912863 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 55: a UniProt-annotated variant site (in)

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-pro55ala (accessed [today's date]).

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