Is DSC3 p.Gly830Ser (c.2488G>A) pathogenic?

DSC3 p.Gly830Ser (c.2488G>A) is classified Conflicting classifications of pathogenicity in DSC3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-01). AlphaMissense: likely benign (0.0908); Rare (popmax 0.331%, afr).

How common is DSC3 p.Gly830Ser (c.2488G>A) in the general population?

DSC3 p.Gly830Ser (c.2488G>A) is rare (popmax 0.331%, afr) (gnomAD).

What do computational predictors say about DSC3 p.Gly830Ser (c.2488G>A)?

AlphaMissense predicts likely benign (score 0.0908) — an in-silico prediction, not a clinical call.

DSC3 p.Gly830Ser

c.2488G>A · rs142851621 · VCV714748

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0908 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.331%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0908	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -5.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	donor loss · deltas
Constraint at this position
Conservation	phyloP 2.5	GERP -0.87, phastCons 0.4
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.331% African / African-American · 248/74,968 alleles

Filtering AF 0.297% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.284%

Overall 0.0184% 297/1,613,492 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.331%	302
Remaining individualsnot grpmax-eligible	0.0288%	3,471
Admixed American	0.0233%	4,285
European (non-Finnish)	0.00136%	73,746
South Asian	0.0011%	91,020

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: DSC3
Protein: p.Gly830Ser
Coding: c.2488G>A
MANE Select: NM_024422 · reported on NM_001941
dbSNP: rs142851621
Type: single nucleotide variant
Location: chr18:30996796 (GRCh38)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 830: a UniProt-annotated variant site (in arvd11; likely pathogenic; mislocalization of dsc2 to the cytoplasm within intercalated disks of the heart)

Full DSC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DSC2 p.Thr830Pro Uncertain significance ★★ ⚠ same residue
DSC2 p.Thr830Ser Uncertain significance ★ ⚠ same residue
DSC2 c.1521-1G>A Likely pathogenic ★★ same type
DSC2 c.1664-1G>A Likely pathogenic ★★ same type
DSC2 c.354+2T>A Likely pathogenic ★★ same type
DSC2 c.355-1G>A Likely pathogenic ★★ same type
DSC2 p.Gln554Ter Pathogenic ★★ same type
DSC2 p.Gln620Ter Pathogenic ★★ same type

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/dsc3-p-gly830ser (accessed [today's date]).

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