Is DSG4 p.Asp226= (c.678C>T) pathogenic?

DSG4 p.Asp226= (c.678C>T) is classified Likely benign in DSG4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-14). Rare (popmax 0.101%, afr); Associated with DSG4-related disorder.

What condition is associated with DSG4 p.Asp226= (c.678C>T)?

DSG4 p.Asp226= (c.678C>T) is associated with DSG4-related disorder (ClinVar).

How common is DSG4 p.Asp226= (c.678C>T) in the general population?

DSG4 p.Asp226= (c.678C>T) is rare (popmax 0.101%, afr) (gnomAD).

DSG4 p.Asp226=

c.678C>T · rs149615937 · VCV3045681

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.101%, afr)

Conditions

DSG4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.4	GERP 1.1, phastCons 1
Overall
CADD	11.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.101% African / African-American · 76/74,976 alleles

Filtering AF 0.083% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0762%

Overall 0.00477% 77/1,613,314 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.101%	987
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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.Asp226=
Coding: c.678C>T
dbSNP: rs149615937
Type: single nucleotide variant
Location: chr18:31390816 (GRCh38)

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

Disease context

DSG4-related disorder

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-asp226 (accessed [today's date]).

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