SCN2A p.Pro614=
c.1842G>T · rs114315466 · VCV130218
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.81%, afr)
Conditions
3
developmental and epileptic encephalopathy, 11
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 -5.8 | GERP -4 |
| Overall | ||
| CADD | 0.281 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.81%
African / African-American · 2,108/75,022 alleles
Filtering AF
2.71%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.67%
Overall
0.165%
2,662/1,614,132 alleles · low-frequency
exomes 1,415/1,461,884 · genomes 1,247/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.81% | 36 |
| Middle Eastern | 0.511% | 196 |
| Remaining individualsnot grpmax-eligible | 0.285% | 351 |
| Admixed American | 0.215% | 465 |
| European (non-Finnish) | 0.0174% | 5,756 |
| South Asian | 0.011% | 9,108 |
| Finnishnot grpmax-eligible | 0.00156% | 64,028 |
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.Pro614=
- Coding
- c.1842G>T
- MANE Select
- NM_001040142
- dbSNP
- rs114315466
- Type
- single nucleotide variant
- Location
- chr2:165323326 (GRCh38)
- Gene constraint
- LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.28 · 5 PDB
- Residue 614
- 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)
Similar variants
- SCN2A p.Pro614Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- SCN2A p.Pro614Thr Uncertain significance ★ ⚠ 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
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-pro614 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown