Is DSG2 p.Pro372= (c.1116C>T) pathogenic?

DSG2 p.Pro372= (c.1116C>T) is classified Likely benign in DSG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). Very rare (popmax 0.00659%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DSG2 p.Pro372= (c.1116C>T)?

DSG2 p.Pro372= (c.1116C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is DSG2 p.Pro372= (c.1116C>T) in the general population?

DSG2 p.Pro372= (c.1116C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

DSG2 p.Pro372=

c.1116C>T · VCV4245038

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Conditions

Cardiovascular phenotype

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 0.098	GERP -2.3, phastCons 0.004
Overall
CADD	10.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,072 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000372% 6/1,614,122 alleles · very rare exomes 5/1,461,826 · genomes 1/152,296 · joint denominator

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: DSG2
Protein: p.Pro372=
Coding: c.1116C>T
MANE Select: NM_001943
Type: single nucleotide variant
Location: chr18:31531088 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 372: an α-helix; the 'interacts with human adenovirus b3 fiber protein' region; the cadherin 3 domain

Full DSG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DSG2 p.Pro372Ser Uncertain significance ★ ⚠ same residue
DSG2 p.Arg46Trp Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Asn266Ser Likely pathogenic ★★ same condition
DSG2 p.Gln873Ter Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Ser404Ter Pathogenic/Likely pathogenic ★★ same condition
DSG2 c.216+3A>C Uncertain significance ★★ same condition
DSG2 c.45+5G>C Uncertain significance ★★ same condition
DSG2 c.46-2A>C Uncertain significance ★★ same condition

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/dsg2-p-pro372 (accessed [today's date]).

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