Is CNTNAP2 p.Pro320Ser (c.958C>T) pathogenic?

CNTNAP2 p.Pro320Ser (c.958C>T) is classified Uncertain significance in CNTNAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). AlphaMissense: likely benign (0.1748); Absent from gnomAD v4.1; Associated with cortical dysplasia-focal epilepsy syndrome.

What condition is associated with CNTNAP2 p.Pro320Ser (c.958C>T)?

CNTNAP2 p.Pro320Ser (c.958C>T) is associated with cortical dysplasia-focal epilepsy syndrome (ClinVar).

How common is CNTNAP2 p.Pro320Ser (c.958C>T) in the general population?

CNTNAP2 p.Pro320Ser (c.958C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNTNAP2 p.Pro320Ser (c.958C>T)?

AlphaMissense predicts likely benign (score 0.1748) — an in-silico prediction, not a clinical call.

CNTNAP2 p.Pro320Ser

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.958C>T · rs113086771 · VCV579019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1748 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cortical dysplasia-focal epilepsy syndrome

Computational evidence

Protein change
AlphaMissense	0.1748	likely benign
REVEL	0.456	indeterminate
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 2,299 kb · p 0.34 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CNTNAP2
Protein: p.Pro320Ser
Coding: c.958C>T
MANE Select: NM_014141
dbSNP: rs113086771
Type: single nucleotide variant
Location: chr7:147128711 (GRCh38)
Gene constraint: LOEUF 0.721 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 83.81 · 1 PDB
Residue 320: the laminin g-like 1 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.Pro320Arg 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
CNTNAP2 p.Gln1111Ter 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-pro320ser (accessed [today's date]).

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