Is CNTN2 p.Pro429= (c.1287C>T) pathogenic?

CNTN2 p.Pro429= (c.1287C>T) is classified Benign/Likely benign in CNTN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-28). Rare (popmax 0.654%, afr); Associated with epilepsy, familial adult myoclonic, 5.

What condition is associated with CNTN2 p.Pro429= (c.1287C>T)?

CNTN2 p.Pro429= (c.1287C>T) is associated with epilepsy, familial adult myoclonic, 5 (ClinVar).

How common is CNTN2 p.Pro429= (c.1287C>T) in the general population?

CNTN2 p.Pro429= (c.1287C>T) is rare (popmax 0.654%, afr) (gnomAD).

CNTN2 p.Pro429=

c.1287C>T · rs145911280 · VCV706995

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.654%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -14	GERP -4.7
Overall
CADD	0.546	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.654% African / African-American · 490/74,886 alleles

Filtering AF 0.606% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.587%

Overall 0.0334% 536/1,606,778 alleles · rare exomes 256/1,454,478 · genomes 280/152,300 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.654%	153
Admixed American	0.0184%	5,430
Remaining individualsnot grpmax-eligible	0.0177%	5,641
East Asian	0.00448%	22,319
European (non-Finnish)	0.00187%	53,373

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.Pro429=
Coding: c.1287C>T
MANE Select: NM_005076
dbSNP: rs145911280
Type: single nucleotide variant
Location: chr1:205064368 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 86.13 · 5 PDB
Residue 429: the ig-like c2-type 5 domain; 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 p.Pro429Leu Uncertain significance ★ ⚠ same residue
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

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-pro429 (accessed [today's date]).

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