Is DSG3 p.Ile960Val (c.2878A>G) pathogenic?

DSG3 p.Ile960Val (c.2878A>G) is classified Benign in DSG3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-06-09). AlphaMissense: likely benign (0.0737); Low-frequency (popmax 4.89%, afr).

How common is DSG3 p.Ile960Val (c.2878A>G) in the general population?

DSG3 p.Ile960Val (c.2878A>G) is low-frequency (popmax 4.89%, afr) (gnomAD).

What do computational predictors say about DSG3 p.Ile960Val (c.2878A>G)?

AlphaMissense predicts likely benign (score 0.0737) — an in-silico prediction, not a clinical call.

DSG3 p.Ile960Val

c.2878A>G · rs73414241 · VCV714871

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0737 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.89%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0737	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -5.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -3.2, phastCons 0.001
Regional constraint	o/e 1.00	unconstrained · MANE · 28 kb · p 1 · regional, not allelic
Overall
CADD	2.564	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 4.89% African / African-American · 3,668/75,038 alleles

Filtering AF 4.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.7%

Overall 0.258% 4,161/1,614,192 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.89%	20
Remaining individualsnot grpmax-eligible	0.325%	308
Admixed American	0.295%	339
Middle Eastern	0.28%	357
South Asian	0.0132%	7,590
European (non-Finnish)	0.00703%	14,217
East Asian	0.00223%	44,886

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.Ile960Val
Coding: c.2878A>G
MANE Select: NM_001944
dbSNP: rs73414241
Type: single nucleotide variant
Location: chr18:31476138 (GRCh38)
Gene constraint: LOEUF 0.862 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.37 · 1 PDB
Residue 960: a UniProt-annotated variant site (in abolm; uncertain significance; loss of expression in skin and mucosa)

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-ile960val (accessed [today's date]).

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