Is DSC3 p.Ser78Thr (c.232T>A) pathogenic?

DSC3 p.Ser78Thr (c.232T>A) is classified Benign in DSC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-11). AlphaMissense: likely benign (0.1097); Common (popmax 73%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DSC3 p.Ser78Thr (c.232T>A)?

AlphaMissense predicts likely benign (score 0.1097) — an in-silico prediction, not a clinical call.

DSC3 p.Ser78Thr

Q: How common is DSC3 p.Ser78Thr (c.232T>A) in the general population?

DSC3 p.Ser78Thr (c.232T>A) is common (popmax 73%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.232T>A · rs276937 · VCV1248384

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1097 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 73%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1097	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP -0.87, phastCons 1
Overall
CADD	17.88	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 73% East Asian · 32,707/44,812 alleles

Filtering AF 72.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 72.1%

Overall 35.3% 568,552/1,612,630 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	73%	1
South Asian	50.6%	2
Finnishnot grpmax-eligible	46.5%	2
Remaining individualsnot grpmax-eligible	36.1%	3
Middle Eastern	35.1%	3
Admixed American	34.4%	3
African / African-American	32.8%	3
European (non-Finnish)	32.3%	3
Amishnot grpmax-eligible	31.9%	3
Ashkenazi Jewishnot grpmax-eligible	31%	3

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.Ser78Thr
Coding: c.232T>A
MANE Select: NM_024422 · reported on NM_001941
dbSNP: rs276937
Type: single nucleotide variant
Location: chr18:31031095 (GRCh38)
Structure: AlphaFold pLDDT 77.26 · 3 PDB

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

Similar variants

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
DSC2 p.Glu127Ter Pathogenic/Likely pathogenic ★★ same type
DSC2 p.Glu593Ter 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-ser78thr (accessed [today's date]).

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