Is CPAP p.Ser1320= (c.3960C>T) pathogenic?

CPAP p.Ser1320= (c.3960C>T) is classified Conflicting classifications of pathogenicity in CPAP (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-06-01). Rare (popmax 0.429%, mid); Associated with Seckel syndrome 4.

What condition is associated with CPAP p.Ser1320= (c.3960C>T)?

CPAP p.Ser1320= (c.3960C>T) is associated with Seckel syndrome 4, microcephaly 6, primary, autosomal recessive (ClinVar).

How common is CPAP p.Ser1320= (c.3960C>T) in the general population?

CPAP p.Ser1320= (c.3960C>T) is rare (popmax 0.429%, mid) (gnomAD).

CPAP p.Ser1320=

c.3960C>T · rs113239817 · VCV311606

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.429%, mid)

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 0.78	GERP -3.7, phastCons 0.96
Overall
CADD	8.079	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.429% Middle Eastern · 26/6,062 alleles

Filtering AF 0.301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.258%

Overall 0.0317% 511/1,613,936 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.429%	233
South Asian	0.276%	363
Admixed American	0.065%	1,538
Ashkenazi Jewishnot grpmax-eligible	0.0642%	1,558
Remaining individualsnot grpmax-eligible	0.0544%	1,838
Finnishnot grpmax-eligible	0.0391%	2,560
East Asian	0.0111%	8,976
African / African-American	0.0107%	9,373
European (non-Finnish)	0.00881%	11,346

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.Ser1320=
Coding: c.3960C>T
MANE Select: NM_018451
dbSNP: rs113239817
Type: single nucleotide variant
Location: chr13:24883234 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 1320: the 'interaction with stil' 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-ser1320 (accessed [today's date]).

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