Is DSG2 p.Val149Phe (c.445G>T) pathogenic?

DSG2 p.Val149Phe (c.445G>T) is classified Uncertain significance in DSG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-24). AlphaMissense: likely pathogenic (0.9492); Absent from gnomAD v4.1; Associated with cardiomyopathy.

What condition is associated with DSG2 p.Val149Phe (c.445G>T)?

DSG2 p.Val149Phe (c.445G>T) is associated with cardiomyopathy (ClinVar).

How common is DSG2 p.Val149Phe (c.445G>T) in the general population?

DSG2 p.Val149Phe (c.445G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSG2 p.Val149Phe (c.445G>T)?

AlphaMissense predicts likely pathogenic (score 0.9492) — an in-silico prediction, not a clinical call.

DSG2 p.Val149Phe

c.445G>T · rs372606274 · VCV1171169

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9492 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.9492	likely pathogenic · top 5% in DSG2
REVEL	0.706	pathogenic-leaning
SaProt	LLR -13.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 48 kb · p 0.014 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: DSG2
Protein: p.Val149Phe
Coding: c.445G>T
MANE Select: NM_001943
dbSNP: rs372606274
Type: single nucleotide variant
Location: chr18:31521165 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 149: the cadherin 1 domain; a β-strand

Full DSG2 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

DSG2 p.Val149Ile Uncertain significance ★★ ⚠ same residue
DSG2 p.Val149= Conflicting classifications of pathogenicity ★ same residue
DSG2 p.Arg46Gln Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Arg46Trp Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Tyr783Ter Pathogenic/Likely pathogenic ★★ same condition
DSG2 c.1014+5G>T Uncertain significance ★★ same condition
DSG2 c.216+3A>C Uncertain significance ★★ same condition
DSG2 c.45+5G>C 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/dsg2-p-val149phe (accessed [today's date]).

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