Is DSC3 p.Ala45Thr (c.133G>A) pathogenic?

DSC3 p.Ala45Thr (c.133G>A) is classified Uncertain significance in DSC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely benign (0.1128); Absent from gnomAD v4.1.

How common is DSC3 p.Ala45Thr (c.133G>A) in the general population?

DSC3 p.Ala45Thr (c.133G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSC3 p.Ala45Thr (c.133G>A)?

AlphaMissense predicts likely benign (score 0.1128) — an in-silico prediction, not a clinical call.

DSC3 p.Ala45Thr

c.133G>A · VCV4662232

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1128 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1128	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -8.24	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 3.2	GERP 2, phastCons 1
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSC3
Protein: p.Ala45Thr
Coding: c.133G>A
MANE Select: NM_024422 · reported on NM_001941
Type: single nucleotide variant
Location: chr18:31032213 (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 p.Ala45= Likely benign ★ same residue
DSC2 p.Ala45fs Pathogenic ★ 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-ala45thr (accessed [today's date]).

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