Is CNTN2 p.Pro974= (c.2922T>G) pathogenic?

CNTN2 p.Pro974= (c.2922T>G) is classified Benign in CNTN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-28). Low-frequency (popmax 3.33%, afr); Associated with epilepsy, familial adult myoclonic, 5.

What condition is associated with CNTN2 p.Pro974= (c.2922T>G)?

CNTN2 p.Pro974= (c.2922T>G) is associated with epilepsy, familial adult myoclonic, 5 (ClinVar).

How common is CNTN2 p.Pro974= (c.2922T>G) in the general population?

CNTN2 p.Pro974= (c.2922T>G) is low-frequency (popmax 3.33%, afr) (gnomAD).

CNTN2 p.Pro974=

c.2922T>G · rs116036521 · VCV474481

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.33%, 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 -13	GERP -4
Overall
CADD	0.457	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.33% African / African-American · 2,494/75,002 alleles

Filtering AF 3.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.17%

Overall 0.178% 2,870/1,614,130 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.33%	30
Admixed American	0.238%	420
Remaining individualsnot grpmax-eligible	0.232%	431
Middle Eastern	0.0825%	1,212
South Asian	0.00878%	11,385
European (non-Finnish)	0.00636%	15,734

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.Pro974=
Coding: c.2922T>G
MANE Select: NM_005076
dbSNP: rs116036521
Type: single nucleotide variant
Location: chr1:205073145 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 86.13 · 5 PDB
Residue 974: the fibronectin type-iii 4 domain

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-pro974 (accessed [today's date]).

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