Is CPAP p.Arg378Ter (c.1132C>T) pathogenic?

CPAP p.Arg378Ter (c.1132C>T) is classified Pathogenic in CPAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-29). Ultra-rare (popmax 0.0164%, mid); Associated with Perisylvian polymicrogyria.

What condition is associated with CPAP p.Arg378Ter (c.1132C>T)?

CPAP p.Arg378Ter (c.1132C>T) is associated with Perisylvian polymicrogyria, microcephaly 6, primary, autosomal recessive, lissencephaly type 3 (ClinVar).

How common is CPAP p.Arg378Ter (c.1132C>T) in the general population?

CPAP p.Arg378Ter (c.1132C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CPAP p.Arg378Ter

c.1132C>T · rs201111299 · VCV503611

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Perisylvian polymicrogyria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -0.55, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00809% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0076%

Overall 0.00793% 128/1,613,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0096%	10,414
European (non-Finnish)	0.00958%	10,442
Admixed American	0.00834%	11,992
African / African-American	0.00267%	37,436
East Asian	0.00223%	44,892

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.Arg378Ter
Coding: c.1132C>T
MANE Select: NM_018451
dbSNP: rs201111299
Type: single nucleotide variant
Location: chr13:24906906 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 378: the 'alpha/beta-tubulin binding' region

Full CPAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Perisylvian polymicrogyria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microcephaly 6, primary, autosomal recessive lissencephaly type 3

Similar variants

CPAP p.Arg1298Gln Likely 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
CPAP p.Ser529Ter 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-arg378ter (accessed [today's date]).

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