Is DSC2 p.Phe58Leu (c.172T>C) pathogenic?

DSC2 p.Phe58Leu (c.172T>C) is classified Likely benign in DSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-28). AlphaMissense: ambiguous (0.4215); Absent from gnomAD v4.1; Associated with cardiomyopathy.

What condition is associated with DSC2 p.Phe58Leu (c.172T>C)?

DSC2 p.Phe58Leu (c.172T>C) is associated with cardiomyopathy (ClinVar).

How common is DSC2 p.Phe58Leu (c.172T>C) in the general population?

DSC2 p.Phe58Leu (c.172T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSC2 p.Phe58Leu (c.172T>C)?

AlphaMissense predicts ambiguous (score 0.4215) — an in-silico prediction, not a clinical call.

DSC2 p.Phe58Leu

c.172T>C · rs138749562 · VCV919180

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4215 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.4215	ambiguous
REVEL	0.063	moderately benign-leaning
SaProt	LLR -2.34	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -1.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.48 · regional, not allelic
Overall
CADD	15.09	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

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: DSC2
Protein: p.Phe58Leu
Coding: c.172T>C
MANE Select: NM_024422
dbSNP: rs138749562
Type: single nucleotide variant
Location: chr18:31092283 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB

Full DSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

DSC2 p.Phe58= Benign/Likely benign ★★ same residue
DSC2 p.Phe58Val Conflicting classifications of pathogenicity ★ ⚠ same residue
DSC2 p.Phe58Cys Uncertain significance ★ ⚠ same residue
DSC2 c.1077+2T>G Uncertain significance ★★ same condition
DSC2 c.1520+4C>T Uncertain significance ★★ same condition
DSC2 c.942+3A>G Uncertain significance ★★ same condition
DSC2 c.942+6A>G Uncertain significance ★★ same condition
DSC2 p.Ala138Ser 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/dsc2-p-phe58leu (accessed [today's date]).

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