Is DSG3 p.Val115= (c.345C>T) pathogenic?

DSG3 p.Val115= (c.345C>T) is classified Benign in DSG3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-09). Common (popmax 19.6%, afr) — too common for a highly-penetrant pathogenic allele.

DSG3 p.Val115=

Q: How common is DSG3 p.Val115= (c.345C>T) in the general population?

DSG3 p.Val115= (c.345C>T) is common (popmax 19.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.345C>T · rs7240789 · VCV1277439

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 19.6%, afr) — too common for a highly-penetrant pathogenic allele

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 -1.4	GERP -3.9, phastCons 0.001
Overall
CADD	1.639	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.6% African / African-American · 14,718/74,916 alleles

Filtering AF 19.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.3%

Overall 2.57% 41,534/1,613,462 alleles · common exomes 31,240/1,461,306 · genomes 10,294/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	19.6%	5
Middle Eastern	5.01%	20
Finnishnot grpmax-eligible	4.31%	23
Remaining individualsnot grpmax-eligible	2.86%	35
Admixed American	2.11%	47
Amishnot grpmax-eligible	1.97%	51
European (non-Finnish)	1.69%	59
South Asian	0.652%	153
Ashkenazi Jewishnot grpmax-eligible	0.382%	262
East Asian	0.00223%	44,872

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.Val115=
Coding: c.345C>T
MANE Select: NM_001944
dbSNP: rs7240789
Type: single nucleotide variant
Location: chr18:31458573 (GRCh38)
Gene constraint: LOEUF 0.862 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.37 · 1 PDB
Residue 115: the cadherin 1 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-val115 (accessed [today's date]).

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