Is CPAP p.Ala677= (c.2031C>T) pathogenic?

CPAP p.Ala677= (c.2031C>T) is classified Benign in CPAP (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-01). Common (popmax 9.96%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Seckel syndrome 4.

What condition is associated with CPAP p.Ala677= (c.2031C>T)?

CPAP p.Ala677= (c.2031C>T) is associated with Seckel syndrome 4, microcephaly 6, primary, autosomal recessive (ClinVar).

CPAP p.Ala677=

Q: How common is CPAP p.Ala677= (c.2031C>T) in the general population?

CPAP p.Ala677= (c.2031C>T) is common (popmax 9.96%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2031C>T · rs61729909 · VCV158199

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 9.96%, eas) — 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 -1.7	GERP -3.7
Overall
CADD	3.897	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.96% East Asian · 4,470/44,870 alleles

Filtering AF 9.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.62%

Overall 0.689% 11,126/1,614,032 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	9.96%	10
African / African-American	3.84%	26
Admixed American	2.75%	36
Middle Eastern	0.924%	108
Remaining individualsnot grpmax-eligible	0.896%	112
Finnishnot grpmax-eligible	0.501%	199
South Asian	0.319%	313
European (non-Finnish)	0.0743%	1,346
Ashkenazi Jewishnot grpmax-eligible	0.0709%	1,410

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.Ala677=
Coding: c.2031C>T
MANE Select: NM_018451
dbSNP: rs61729909
Type: single nucleotide variant
Location: chr13:24906007 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 677: 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.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-ala677 (accessed [today's date]).

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