Is DSC1 p.Thr710= (c.2130A>G) pathogenic?

DSC1 p.Thr710= (c.2130A>G) is classified Benign in DSC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-27). Common (popmax 8.88%, afr) — too common for a highly-penetrant pathogenic allele.

DSC1 p.Thr710=

Q: How common is DSC1 p.Thr710= (c.2130A>G) in the general population?

DSC1 p.Thr710= (c.2130A>G) is common (popmax 8.88%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2130A>G · rs16961338 · VCV789105

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.88%, afr) — too common for a highly-penetrant pathogenic allele

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 -1.3	GERP -3.7, phastCons 0.001
Overall
CADD	5.974	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.88% African / African-American · 6,649/74,904 alleles

Filtering AF 8.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.63%

Overall 0.457% 7,368/1,612,596 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.88%	11
Remaining individualsnot grpmax-eligible	0.524%	191
Admixed American	0.406%	246
Middle Eastern	0.281%	356
South Asian	0.0165%	6,063
European (non-Finnish)	0.00984%	10,166
East Asian	0.00223%	44,790

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: DSC1
Protein: p.Thr710=
Coding: c.2130A>G
MANE Select: NM_024421
dbSNP: rs16961338
Type: single nucleotide variant
Location: chr18:31132676 (GRCh38)
Gene constraint: LOEUF 0.951 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.16 · 1 PDB

Full DSC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DSC1 p.Ile200Thr Benign ★★ ⚠ same type
DSC1 p.Met659Arg Benign ★★ same type
DSC1 p.Ala128Pro Uncertain significance ★ ⚠ same type
DSC1 p.Ala209Val Uncertain significance ★ ⚠ same type
DSC1 p.Ala221Glu Uncertain significance ★ ⚠ same type
DSC1 p.Ala239Thr Uncertain significance ★ ⚠ same type
DSC1 p.Ala574Thr Uncertain significance ★ ⚠ same type
DSC1 p.Ala693Val Uncertain significance ★ ⚠ 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/dsc1-p-thr710 (accessed [today's date]).

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