Is SCN5A p.Arg620= (c.1860C>T) pathogenic?

SCN5A p.Arg620= (c.1860C>T) is classified Likely benign in SCN5A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-15). Very rare (popmax 8.78e-05%, nfe); Associated with cardiac rhythm disease.

What condition is associated with SCN5A p.Arg620= (c.1860C>T)?

SCN5A p.Arg620= (c.1860C>T) is associated with cardiac rhythm disease (ClinVar).

How common is SCN5A p.Arg620= (c.1860C>T) in the general population?

SCN5A p.Arg620= (c.1860C>T) is very rare (popmax 8.78e-05%, nfe) (gnomAD).

SCN5A p.Arg620=

c.1860C>T · rs1460093851 · VCV925361

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.78e-05%, nfe)

Conditions

cardiac rhythm disease

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 0.48	GERP -2.3, phastCons 0.027
Overall
CADD	2.252	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.78e-05% European (non-Finnish) · 1/1,138,870 alleles

Overall 0.000145% 2/1,381,564 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00169%	59,012
European (non-Finnish)grpmax	8.78e-05%	1,138,870

Remaining individuals 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: SCN5A
Protein: p.Arg620=
Coding: c.1860C>T
MANE Select: NM_000335
dbSNP: rs1460093851
Type: single nucleotide variant
Location: chr3:38603742 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.02 · 16 PDB
Residue 620: a UniProt-annotated variant site (in brgda1; uncertain significance)

Full SCN5A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardiac rhythm disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCN5A p.Arg620Cys Uncertain significance ★★ ⚠ same residue
SCN5A p.Arg620His Uncertain significance ★★ ⚠ same residue
SCN5A p.Arg620Leu Uncertain significance ★★ ⚠ same residue
SCN5A c.1338+2T>A Pathogenic/Likely pathogenic ★★ same condition
SCN5A c.2263-2A>G Likely pathogenic ★★ same condition
SCN5A c.3508+1G>T Likely pathogenic ★★ same condition
SCN5A c.3837+1G>A Pathogenic ★★ same condition
SCN5A c.4242+1G>C Pathogenic/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/scn5a-p-arg620 (accessed [today's date]).

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