Is CNTN2 p.Val1024Ile (c.3070G>A) pathogenic?

CNTN2 p.Val1024Ile (c.3070G>A) is classified Benign in CNTN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.108); Common (popmax 13%, sas) — too common for a highly-penetrant pathogenic allele; Associated with epilepsy, familial adult myoclonic, 5.

What condition is associated with CNTN2 p.Val1024Ile (c.3070G>A)?

CNTN2 p.Val1024Ile (c.3070G>A) is associated with epilepsy, familial adult myoclonic, 5 (ClinVar).

What do computational predictors say about CNTN2 p.Val1024Ile (c.3070G>A)?

AlphaMissense predicts likely benign (score 0.108) — an in-silico prediction, not a clinical call.

CNTN2 p.Val1024Ile

Q: How common is CNTN2 p.Val1024Ile (c.3070G>A) in the general population?

CNTN2 p.Val1024Ile (c.3070G>A) is common (popmax 13%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3070G>A · rs17416074 · VCV1166971

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.108 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 13%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

epilepsy, familial adult myoclonic, 5

Computational evidence

Protein change
AlphaMissense	0.108	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.7	GERP -4.2
Regional constraint	o/e 0.79	unconstrained · MANE · 21 kb · p 1.7e-15 · regional, not allelic
Overall
CADD	0.003	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13% South Asian · 11,868/91,070 alleles

Filtering AF 12.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.8%

Overall 4.07% 65,623/1,613,920 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	13%	8
Finnishnot grpmax-eligible	9.57%	10
African / African-American	8.62%	12
Ashkenazi Jewishnot grpmax-eligible	8.18%	12
Middle Eastern	5.1%	20
Remaining individualsnot grpmax-eligible	4.45%	22
Admixed American	2.88%	35
European (non-Finnish)	2.85%	35
Amishnot grpmax-eligible	1.76%	57
East Asian	0.675%	148

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.Val1024Ile
Coding: c.3070G>A
MANE Select: NM_005076
dbSNP: rs17416074
Type: single nucleotide variant
Location: chr1:205073712 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 86.13 · 5 PDB
Residue 1024: a UniProt-annotated variant site (in)

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.Val1024= Likely benign ★ 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-val1024ile (accessed [today's date]).

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