Is DSG4 p.Val199Ile (c.595G>A) pathogenic?

DSG4 p.Val199Ile (c.595G>A) is classified Likely benign in DSG4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-16). AlphaMissense: likely benign (0.0549); Ultra-rare (popmax 0.0834%, amr); Associated with Inborn genetic diseases.

What condition is associated with DSG4 p.Val199Ile (c.595G>A)?

DSG4 p.Val199Ile (c.595G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSG4 p.Val199Ile (c.595G>A) in the general population?

DSG4 p.Val199Ile (c.595G>A) is ultra-rare (popmax 0.0834%, amr) (gnomAD).

What do computational predictors say about DSG4 p.Val199Ile (c.595G>A)?

AlphaMissense predicts likely benign (score 0.0549) — an in-silico prediction, not a clinical call.

DSG4 p.Val199Ile

c.595G>A · rs139019059 · VCV2211872

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0549 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0834%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0549	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.35	GERP -4
Regional constraint	o/e 1.07	unconstrained · MANE · 37 kb · p 0.015 · regional, not allelic
Overall
CADD	0.363	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 0.0834% Admixed American · 50/59,944 alleles

Filtering AF 0.0649% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0584%

Overall 0.00874% 141/1,613,630 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0834%	1,199
Remaining individualsnot grpmax-eligible	0.0144%	6,940
European (non-Finnish)	0.00653%	15,322
African / African-American	0.00401%	24,963
East Asian	0.00223%	44,864
South Asian	0.0011%	91,076

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.Val199Ile
Coding: c.595G>A
dbSNP: rs139019059
Type: single nucleotide variant
Location: chr18:31390733 (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-val199ile (accessed [today's date]).

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