Is CPAP p.Pro627= (c.1881G>A) pathogenic?

CPAP p.Pro627= (c.1881G>A) is classified Benign in CPAP (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Common (popmax 18.3%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Seckel syndrome 4.

What condition is associated with CPAP p.Pro627= (c.1881G>A)?

CPAP p.Pro627= (c.1881G>A) is associated with Seckel syndrome 4, microcephaly 6, primary, autosomal recessive (ClinVar).

CPAP p.Pro627=

Q: How common is CPAP p.Pro627= (c.1881G>A) in the general population?

CPAP p.Pro627= (c.1881G>A) is common (popmax 18.3%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1881G>A · rs75985315 · VCV95909

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 18.3%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

Seckel syndrome 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -3.7
Overall
CADD	0.464	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.3% Admixed American · 10,998/59,970 alleles

Filtering AF 18.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.9%

Overall 1.08% 17,406/1,613,606 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	18.3%	5
East Asian	9.56%	10
Remaining individualsnot grpmax-eligible	1.03%	97
Ashkenazi Jewishnot grpmax-eligible	0.94%	106
South Asian	0.331%	302
Middle Eastern	0.264%	379
African / African-American	0.243%	412
European (non-Finnish)	0.0587%	1,705
Finnishnot grpmax-eligible	0.00781%	12,803

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.Pro627=
Coding: c.1881G>A
MANE Select: NM_018451
dbSNP: rs75985315
Type: single nucleotide variant
Location: chr13:24906157 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 627: the 'disordered' region

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.Pro627Leu Uncertain significance ★★ ⚠ 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
CPAP p.Glu212Ter 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-pro627 (accessed [today's date]).

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