Is DSG4 p.Ile34Val (c.100A>G) pathogenic?

DSG4 p.Ile34Val (c.100A>G) is classified Uncertain significance in DSG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely benign (0.0628); Ultra-rare (popmax 0.025%, amr); Associated with Inborn genetic diseases.

What condition is associated with DSG4 p.Ile34Val (c.100A>G)?

DSG4 p.Ile34Val (c.100A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DSG4 p.Ile34Val (c.100A>G) in the general population?

DSG4 p.Ile34Val (c.100A>G) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about DSG4 p.Ile34Val (c.100A>G)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

DSG4 p.Ile34Val

c.100A>G · rs201146453 · VCV2400701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -5.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.036	GERP -1.9
Regional constraint	o/e 1.07	unconstrained · MANE · 37 kb · p 0.015 · regional, not allelic
Overall
CADD	9.201	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 0.025% Admixed American · 15/59,978 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00112% 18/1,613,288 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	3,999
Remaining individualsnot grpmax-eligible	0.0032%	31,226
European (non-Finnish)	8.48e-05%	1,179,334

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.Ile34Val
Coding: c.100A>G
dbSNP: rs201146453
Type: single nucleotide variant
Location: chr18:31386703 (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-ile34val (accessed [today's date]).

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