Is CNTN2 p.Phe129= (c.387C>T) pathogenic?

CNTN2 p.Phe129= (c.387C>T) is classified Likely benign in CNTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-05). Very rare (popmax 0.00139%, afr); Associated with epilepsy, familial adult myoclonic, 5.

What condition is associated with CNTN2 p.Phe129= (c.387C>T)?

CNTN2 p.Phe129= (c.387C>T) is associated with epilepsy, familial adult myoclonic, 5 (ClinVar).

How common is CNTN2 p.Phe129= (c.387C>T) in the general population?

CNTN2 p.Phe129= (c.387C>T) is very rare (popmax 0.00139%, afr) (gnomAD).

CNTN2 p.Phe129=

c.387C>T · rs957164200 · VCV2731976

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00139%, afr)

Conditions

epilepsy, familial adult myoclonic, 5

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 -14	GERP -4.4
Overall
CADD	1.468	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00139% African / African-American · 1/72,196 alleles

Filtering AF 0.000716% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00056%

Overall 0.000984% 15/1,524,956 alleles · very rare exomes 15/1,373,084 · genomes 0/151,872 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00139%	72,196
European (non-Finnish)	0.00123%	81,057

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: CNTN2
Protein: p.Phe129=
Coding: c.387C>T
MANE Select: NM_005076
dbSNP: rs957164200
Type: single nucleotide variant
Location: chr1:205058352 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 86.13 · 5 PDB
Residue 129: a β-strand

Full CNTN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epilepsy, familial adult myoclonic, 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNTN2 c.1241-1G>C Likely pathogenic ★★ same condition
CNTN2 c.2432-2A>G Likely pathogenic ★★ same condition
CNTN2 p.Arg140Ter Pathogenic/Likely pathogenic ★★ same condition
CNTN2 p.Arg314Ter Pathogenic ★★ same condition
CNTN2 p.Trp731Ter Pathogenic/Likely pathogenic ★★ same condition
CNTN2 c.2196+5G>A Uncertain significance ★★ same condition
CNTN2 p.Ala230Val Uncertain significance ★★ ⚠ same condition
CNTN2 p.Ala263Thr Uncertain significance ★★ ⚠ 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/cntn2-p-phe129 (accessed [today's date]).

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