Is DSG2 p.Asp162Val (c.485A>T) pathogenic?

DSG2 p.Asp162Val (c.485A>T) is classified Uncertain significance in DSG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely benign (0.176); Very rare (popmax 8.48e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DSG2 p.Asp162Val (c.485A>T)?

DSG2 p.Asp162Val (c.485A>T) is associated with Cardiovascular phenotype (ClinVar).

How common is DSG2 p.Asp162Val (c.485A>T) in the general population?

DSG2 p.Asp162Val (c.485A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DSG2 p.Asp162Val (c.485A>T)?

AlphaMissense predicts likely benign (score 0.176) — an in-silico prediction, not a clinical call.

DSG2 p.Asp162Val

c.485A>T · VCV4245039

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.176 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.176	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -11.58	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 48 kb · p 0.014 · regional, not allelic
Overall
CADD	24.0	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 8.48e-05% European (non-Finnish) · 1/1,179,684 alleles

Overall 6.84e-05% 1/1,461,596 alleles · very rare

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: DSG2
Protein: p.Asp162Val
Coding: c.485A>T
MANE Select: NM_001943
Type: single nucleotide variant
Location: chr18:31521205 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 162: the cadherin 2 domain; a β-strand

Full DSG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

DSG2 p.Asp162Asn Uncertain significance ★ ⚠ same residue
DSG2 p.Asp162Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
DSG2 p.Asp162fs Pathogenic ★ same residue
DSG2 p.Asp162Tyr Uncertain significance ★ ⚠ same residue
DSG2 p.Asp162= Likely benign ★ same residue
DSG2 p.Arg46Trp Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Asn266Ser Likely pathogenic ★★ same condition
DSG2 p.Gln873Ter Pathogenic/Likely pathogenic ★★ 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-asp162val (accessed [today's date]).

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