Is DSG1 p.Phe385= (c.1155T>C) pathogenic?

DSG1 p.Phe385= (c.1155T>C) is classified Likely benign in DSG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-23). Very rare (popmax 0.00373%, nfe).

How common is DSG1 p.Phe385= (c.1155T>C) in the general population?

DSG1 p.Phe385= (c.1155T>C) is very rare (popmax 0.00373%, nfe) (gnomAD).

DSG1 p.Phe385=

c.1155T>C · rs768303232 · VCV758701

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP -1.1, phastCons 1
Overall
CADD	8.584	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00373% European (non-Finnish) · 44/1,179,964 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00328% 53/1,613,960 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,619
European (non-Finnish)grpmax	0.00373%	26,817
Admixed American	0.00333%	30,002
South Asian	0.00329%	30,363

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DSG1
Protein: p.Phe385=
Coding: c.1155T>C
MANE Select: NM_001942
dbSNP: rs768303232
Type: single nucleotide variant
Location: chr18:31336503 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.93
Residue 385: the 'required for interaction with erbin' region; a UniProt-annotated variant site (in ppks1; uncertain significance; reduces expression of krt10 in keratinocytes); a UniProt-annotated variant site (in ppks1; uncertain significance; reduces protein expression, expression of krt10 and loricrin and increases phosphorylated erk in keratinocytes); the cadherin 3 domain

Full DSG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DSG1 p.Phe385Ser Uncertain significance ★ ⚠ same residue
DSG1 p.Arg128Ter Pathogenic ★★ same type
DSG1 p.Arg144Ter Pathogenic ★★ same type
DSG1 p.Arg219Ter Pathogenic ★★ same type
DSG1 p.Arg242Ter Pathogenic ★★ same type
DSG1 p.Arg26Ter Pathogenic ★★ same type
DSG1 p.Arg45Ter Pathogenic/Likely pathogenic ★★ same type
DSG1 p.Arg887Ter Pathogenic/Likely pathogenic ★★ same type

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/dsg1-p-phe385 (accessed [today's date]).

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