Is DSG3 p.Val896Phe (c.2686G>T) pathogenic?

DSG3 p.Val896Phe (c.2686G>T) is classified Uncertain significance in DSG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). AlphaMissense: likely benign (0.0752); Absent from gnomAD v4.1.

How common is DSG3 p.Val896Phe (c.2686G>T) in the general population?

DSG3 p.Val896Phe (c.2686G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSG3 p.Val896Phe (c.2686G>T)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

DSG3 p.Val896Phe

c.2686G>T · rs2510898061 · VCV2290708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -7.77	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 0.57	GERP -2.4
Regional constraint	o/e 1.00	unconstrained · MANE · 28 kb · p 1 · regional, not allelic
Overall
CADD	1.642	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSG3
Protein: p.Val896Phe
Coding: c.2686G>T
MANE Select: NM_001944
dbSNP: rs2510898061
Type: single nucleotide variant
Location: chr18:31475946 (GRCh38)
Gene constraint: LOEUF 0.862 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.37 · 1 PDB
Residue 896: 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-val896phe (accessed [today's date]).

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