Is CNTNAP2 p.Arg900= (c.2698C>A) pathogenic?

CNTNAP2 p.Arg900= (c.2698C>A) is classified Conflicting classifications of pathogenicity in CNTNAP2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-17). Ultra-rare (popmax 0.0165%, mid); Associated with cortical dysplasia-focal epilepsy syndrome.

What condition is associated with CNTNAP2 p.Arg900= (c.2698C>A)?

CNTNAP2 p.Arg900= (c.2698C>A) is associated with cortical dysplasia-focal epilepsy syndrome (ClinVar).

How common is CNTNAP2 p.Arg900= (c.2698C>A) in the general population?

CNTNAP2 p.Arg900= (c.2698C>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CNTNAP2 p.Arg900=

Q: How is CNTNAP2-related developmental and epileptic encephalopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2698C>A · rs375318010 · VCV95564

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

cortical dysplasia-focal epilepsy syndrome

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 4	GERP 2, phastCons 1
Overall
CADD	11.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.00124% 20/1,614,040 alleles · ultra-rare exomes 19/1,461,880 · genomes 1/152,160 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.0112%	8,929
East Asian	0.00223%	44,852
South Asian	0.0011%	91,076
European (non-Finnish)	0.000847%	118,001

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: CNTNAP2
Protein: p.Arg900=
Coding: c.2698C>A
MANE Select: NM_014141
dbSNP: rs375318010
Type: single nucleotide variant
Location: chr7:148147634 (GRCh38)
Gene constraint: LOEUF 0.721 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 83.81 · 1 PDB
Residue 900: the laminin g-like 3 domain

Full CNTNAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cortical dysplasia-focal epilepsy syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CNTNAP2-related developmental and epileptic encephalopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CNTNAP2 p.Arg900Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CNTNAP2 p.Arg900Trp Uncertain significance ★ ⚠ same residue
CNTNAP2 c.1348+1G>A Likely pathogenic ★★ same condition
CNTNAP2 c.3382-2A>C Likely pathogenic ★★ same condition
CNTNAP2 c.97+1G>A Pathogenic/Likely pathogenic ★★ same condition
CNTNAP2 p.Arg1088Ter Pathogenic/Likely pathogenic ★★ same condition
CNTNAP2 p.Arg1095Ter Pathogenic/Likely pathogenic ★★ same condition
CNTNAP2 p.Arg483Ter 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/cntnap2-p-arg900 (accessed [today's date]).

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