Is SCN9A p.Pro613= (c.1839G>A) pathogenic?

SCN9A p.Pro613= (c.1839G>A) is classified Likely benign in SCN9A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-27). Ultra-rare (popmax 0.0111%, eas); Associated with neuropathy, hereditary sensory and autonomic, type 2A.

What condition is associated with SCN9A p.Pro613= (c.1839G>A)?

SCN9A p.Pro613= (c.1839G>A) is associated with neuropathy, hereditary sensory and autonomic, type 2A, generalized epilepsy with febrile seizures plus, type 7 (ClinVar).

How common is SCN9A p.Pro613= (c.1839G>A) in the general population?

SCN9A p.Pro613= (c.1839G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

SCN9A p.Pro613=

Q: How is Hereditary sensory and autonomic neuropathy type 2 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1839G>A · rs565711085 · VCV2923113

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Conditions

neuropathy, hereditary sensory and autonomic, type 2A

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -5.1	GERP -5
Overall
CADD	10.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,870 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00105% 17/1,614,062 alleles · ultra-rare exomes 15/1,461,788 · genomes 2/152,274 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,974
Admixed American	0.00167%	60,016
South Asian	0.0011%	91,082
European (non-Finnish)	0.000847%	117,995

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: SCN9A
Protein: p.Pro613=
Coding: c.1839G>A
MANE Select: NM_001365536
dbSNP: rs565711085
Type: single nucleotide variant
Location: chr2:166284588 (GRCh38)

Full SCN9A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuropathy, hereditary sensory and autonomic, type 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: generalized epilepsy with febrile seizures plus, type 7

For Hereditary sensory and autonomic neuropathy type 2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

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/scn9a-p-pro613 (accessed [today's date]).

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