Is SCN4B p.Ser30= (c.90G>T) pathogenic?

SCN4B p.Ser30= (c.90G>T) is classified Uncertain significance in SCN4B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-13). Very rare (popmax 0.000169%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with SCN4B p.Ser30= (c.90G>T)?

SCN4B p.Ser30= (c.90G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is SCN4B p.Ser30= (c.90G>T) in the general population?

SCN4B p.Ser30= (c.90G>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

SCN4B p.Ser30=

c.90G>T · rs1948156331 · VCV1765811

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.39	acceptor gain · deltas
Pangolin	Δ0.37	gain · loss 0.21 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -6	GERP -4.1
Overall
CADD	15.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,974 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,958 alleles · very rare exomes 2/1,461,884 · genomes 0/152,074 · joint denominator

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: SCN4B
Protein: p.Ser30=
Coding: c.90G>T
MANE Select: NM_174934
dbSNP: rs1948156331
Type: single nucleotide variant
Location: chr11:118145201 (GRCh38)
Gene constraint: LOEUF 1.324 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91 · 5 PDB

Full SCN4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCN4B c.463+3A>T Uncertain significance ★★ same condition
SCN4B c.594-2A>G Uncertain significance ★★ same condition
SCN4B c.62-1G>A Uncertain significance ★★ same condition
SCN4B p.Ala12Thr Uncertain significance ★★ ⚠ same condition
SCN4B p.Arg195Trp Uncertain significance ★★ ⚠ same condition
SCN4B p.Arg67Gln Uncertain significance ★★ ⚠ same condition
SCN4B p.Asp159His Uncertain significance ★★ ⚠ same condition
SCN4B p.Gly214Val 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/scn4b-p-ser30 (accessed [today's date]).

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