Is SCN2A p.Ser985= (c.2955C>T) pathogenic?

SCN2A p.Ser985= (c.2955C>T) is classified Conflicting classifications of pathogenicity in SCN2A (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0638%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SCN2A p.Ser985= (c.2955C>T)?

SCN2A p.Ser985= (c.2955C>T) is associated with Inborn genetic diseases, seizures, benign familial infantile, 3, developmental and epileptic encephalopathy, 11 (ClinVar).

How common is SCN2A p.Ser985= (c.2955C>T) in the general population?

SCN2A p.Ser985= (c.2955C>T) is ultra-rare (popmax 0.0638%, nfe) (gnomAD).

SCN2A p.Ser985=

c.2955C>T · rs149859004 · VCV139009

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0638%, nfe)

Conditions

Inborn genetic diseases

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 -2.6	GERP -1.5
Overall
CADD	4.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0638% European (non-Finnish) · 753/1,179,984 alleles

Filtering AF 0.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0585%

Overall 0.148% 2,392/1,614,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.29%	44
Remaining individualsnot grpmax-eligible	0.178%	563
Ashkenazi Jewishnot grpmax-eligible	0.132%	759
European (non-Finnish)grpmax	0.0638%	1,567
East Asian	0.0357%	2,803
Admixed American	0.00667%	15,004
South Asian	0.00439%	22,766
African / African-American	0.00267%	37,521

Finnish 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: SCN2A
Protein: p.Ser985=
Coding: c.2955C>T
MANE Select: NM_001040142
dbSNP: rs149859004
Type: single nucleotide variant
Location: chr2:165354227 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.28 · 5 PDB
Residue 985: a UniProt-annotated variant site (found in a patient with intractable epilepsy and severe mental decline; likely pathogenic; non-conducting; loss of voltage-gated sodium channel activity; dominant-negative); a UniProt-annotated variant site (found in a patient with schizofrenia; uncertain significance); a UniProt-annotated variant site (found in a patient with autism spectrum disorder; likely pathogenic); a UniProt-annotated variant site (found in a patient with autism spectrum disorder; likely pathogenic; loss of voltage-gated sodium channel activity; non-conducting); an α-helix

Full SCN2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: seizures, benign familial infantile, 3 developmental and epileptic encephalopathy, 11

Similar variants

SCN2A p.Ser985Phe Likely pathogenic same residue
SCN2A p.Ala1773Thr Pathogenic ★★★ same condition
SCN2A p.Arg220Gly Likely pathogenic ★★★ same condition
SCN2A p.Arg853Gln Pathogenic ★★★ same condition
SCN2A p.Gly899Asp Likely pathogenic ★★★ same condition
SCN2A p.Leu1611Pro Pathogenic ★★★ same condition
SCN2A p.Leu886Ser Likely pathogenic ★★★ same condition
SCN2A p.Lys1260Glu Likely pathogenic ★★★ 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/scn2a-p-ser985 (accessed [today's date]).

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