Is DSG4 p.Ala342Val (c.1025C>T) pathogenic?

DSG4 p.Ala342Val (c.1025C>T) is classified Uncertain significance in DSG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.0616); Ultra-rare (popmax 0.0653%, afr); Associated with Inborn genetic diseases.

What condition is associated with DSG4 p.Ala342Val (c.1025C>T)?

DSG4 p.Ala342Val (c.1025C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSG4 p.Ala342Val (c.1025C>T) in the general population?

DSG4 p.Ala342Val (c.1025C>T) is ultra-rare (popmax 0.0653%, afr) (gnomAD).

What do computational predictors say about DSG4 p.Ala342Val (c.1025C>T)?

AlphaMissense predicts likely benign (score 0.0616) — an in-silico prediction, not a clinical call.

DSG4 p.Ala342Val

c.1025C>T · rs112376128 · VCV2344805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0616 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0653%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0616	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -5.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.13	GERP -3.2
Regional constraint	o/e 1.07	unconstrained · MANE · 37 kb · p 0.015 · regional, not allelic
Overall
CADD	7.756	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

Grpmax group 0.0653% African / African-American · 49/75,026 alleles

Filtering AF 0.0507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0455%

Overall 0.00489% 79/1,613,974 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0653%	1,531
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Admixed American	0.0117%	8,572
European (non-Finnish)	8.48e-05%	1,179,924

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: DSG4
Protein: p.Ala342Val
Coding: c.1025C>T
dbSNP: rs112376128
Type: single nucleotide variant
Location: chr18:31399291 (GRCh38)

Full DSG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/dsg4-p-ala342val (accessed [today's date]).

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