Is CNTN2 p.Ser920= (c.2760C>T) pathogenic?

CNTN2 p.Ser920= (c.2760C>T) is classified Likely benign in CNTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-09). Ultra-rare (popmax 0.0164%, mid); Associated with epilepsy, familial adult myoclonic, 5.

What condition is associated with CNTN2 p.Ser920= (c.2760C>T)?

CNTN2 p.Ser920= (c.2760C>T) is associated with epilepsy, familial adult myoclonic, 5 (ClinVar).

How common is CNTN2 p.Ser920= (c.2760C>T) in the general population?

CNTN2 p.Ser920= (c.2760C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CNTN2 p.Ser920=

c.2760C>T · rs201621031 · VCV1110908

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -0.3	GERP -4.6, phastCons 0.098
Overall
CADD	4.868	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00818% 132/1,614,086 alleles · ultra-rare exomes 117/1,461,858 · genomes 15/152,228 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.267%	375
Remaining individualsnot grpmax-eligible	0.0256%	3,905
Middle Easterngrpmax	0.0164%	6,082
Admixed American	0.01%	10,001
African / African-American	0.00267%	37,468
European (non-Finnish)	0.00237%	42,145

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser920=
Coding: c.2760C>T
MANE Select: NM_005076
dbSNP: rs201621031
Type: single nucleotide variant
Location: chr1:205072511 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 86.13 · 5 PDB
Residue 920: 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-ser920 (accessed [today's date]).

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