Is SCN3A p.Pro282Ser (c.844C>T) pathogenic?

SCN3A p.Pro282Ser (c.844C>T) is classified Uncertain significance in SCN3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-19). AlphaMissense: likely benign (0.184); Very rare (popmax 0.00229%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SCN3A p.Pro282Ser (c.844C>T)?

SCN3A p.Pro282Ser (c.844C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SCN3A p.Pro282Ser (c.844C>T) in the general population?

SCN3A p.Pro282Ser (c.844C>T) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about SCN3A p.Pro282Ser (c.844C>T)?

AlphaMissense predicts likely benign (score 0.184) — an in-silico prediction, not a clinical call.

SCN3A p.Pro282Ser

c.844C>T · rs771403348 · VCV858585

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.184 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.184	likely benign
REVEL	0.557	indeterminate
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 441 bp · p 0.9 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,180,006 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00173% 28/1,614,004 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,704
African / African-American	0.00133%	74,914

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: SCN3A
Protein: p.Pro282Ser
Coding: c.844C>T
MANE Select: NM_006922
dbSNP: rs771403348
Type: single nucleotide variant
Location: chr2:165162679 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.76 · 2 PDB

Full SCN3A 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

Similar variants

SCN3A p.Phe1646Ser Likely pathogenic ★★ same condition
SCN3A p.Val1769Ala Likely pathogenic ★★ same condition
SCN3A c.694+5G>C Uncertain significance ★★ same condition
SCN3A p.Ala1512Glu Uncertain significance ★★ ⚠ same condition
SCN3A p.Ala1905Thr Uncertain significance ★★ ⚠ same condition
SCN3A p.Ala34Gly Uncertain significance ★★ ⚠ same condition
SCN3A p.Ala459Asp Uncertain significance ★★ ⚠ same condition
SCN3A p.Arg1032Thr 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/scn3a-p-pro282ser (accessed [today's date]).

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