Is DSG4 p.Pro95Ser (c.283C>T) pathogenic?

DSG4 p.Pro95Ser (c.283C>T) is classified Uncertain significance in DSG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely benign (0.3281); Very rare (popmax 0.00334%, amr); Associated with Inborn genetic diseases.

What condition is associated with DSG4 p.Pro95Ser (c.283C>T)?

DSG4 p.Pro95Ser (c.283C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSG4 p.Pro95Ser (c.283C>T) in the general population?

DSG4 p.Pro95Ser (c.283C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about DSG4 p.Pro95Ser (c.283C>T)?

AlphaMissense predicts likely benign (score 0.3281) — an in-silico prediction, not a clinical call.

DSG4 p.Pro95Ser

c.283C>T · VCV3842670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3281 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3281	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 37 kb · p 0.015 · regional, not allelic
Overall
CADD	23.9	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 0.00334% Admixed American · 2/59,944 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,613,438 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,972
European (non-Finnish)	8.48e-05%	1,179,633

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.Pro95Ser
Coding: c.283C>T
Type: single nucleotide variant
Location: chr18:31388433 (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-pro95ser (accessed [today's date]).

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