Is DSG3 p.Pro369Ser (c.1105C>T) pathogenic?

DSG3 p.Pro369Ser (c.1105C>T) is classified Uncertain significance in DSG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.1105); Very rare (popmax 0.00329%, sas).

How common is DSG3 p.Pro369Ser (c.1105C>T) in the general population?

DSG3 p.Pro369Ser (c.1105C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about DSG3 p.Pro369Ser (c.1105C>T)?

AlphaMissense predicts likely benign (score 0.1105) — an in-silico prediction, not a clinical call.

DSG3 p.Pro369Ser

c.1105C>T · VCV4245056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1105 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1105	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -10.07	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.42	GERP 2
Regional constraint	o/e 1.00	unconstrained · MANE · 28 kb · p 1 · regional, not allelic
Overall
CADD	20.7	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 0.00329% South Asian · 3/91,070 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000496% 8/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,357
European (non-Finnish)	0.000424%	236,004

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: DSG3
Protein: p.Pro369Ser
Coding: c.1105C>T
MANE Select: NM_001944
Type: single nucleotide variant
Location: chr18:31464216 (GRCh38)
Gene constraint: LOEUF 0.862 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.37 · 1 PDB
Residue 369: a UniProt-annotated variant site (in abolm; uncertain significance; loss of expression in skin and mucosa); a β-strand; the cadherin 3 domain

Full DSG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DSG3 p.Leu856Val Uncertain significance ★★ ⚠ same type
DSG3 c.1272-24G>A Benign ★★ same type
DSG3 c.1412-63T>G Benign ★★ same type
DSG3 c.1412-92T>C Benign ★★ same type
DSG3 c.1412-95G>A Benign ★★ same type
DSG3 c.1637-34C>T Benign ★★ same type
DSG3 c.1897+60A>G Benign ★★ same type
DSG3 c.2101+132G>C Benign ★★ 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/dsg3-p-pro369ser (accessed [today's date]).

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