Is DLG2 p.Ile897Phe (c.2689A>T) pathogenic?

DLG2 p.Ile897Phe (c.2689A>T) is classified Uncertain significance in DLG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely pathogenic (0.9548); Absent from gnomAD v4.1.

How common is DLG2 p.Ile897Phe (c.2689A>T) in the general population?

DLG2 p.Ile897Phe (c.2689A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLG2 p.Ile897Phe (c.2689A>T)?

AlphaMissense predicts likely pathogenic (score 0.9548) — an in-silico prediction, not a clinical call.

DLG2 p.Ile897Phe

c.2689A>T · VCV4660345

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9548 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9548	likely pathogenic
REVEL	0.301	indeterminate
SaProt	LLR -14.36	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 374 kb · p 4.3e-10 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I792F vs ClinVar I897F) — verify the residue.

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: DLG2
Protein: p.Ile897Phe
Coding: c.2689A>T
MANE Select: NM_001142699
Type: single nucleotide variant
Location: chr11:83466748 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 69.93 · 2 PDB

Full DLG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLG2 p.Arg797= Benign ★★ same type
DLG2 p.Gln944= Benign ★★ same type
DLG2 p.Leu459= Benign ★★ same type
DLG2 p.Leu514Pro Likely benign ★★ same type
DLG2 p.Lys59= Benign ★★ same type
DLG2 p.Ser804= Benign/Likely benign ★★ same type
DLG2 c.624+1G>A Uncertain significance ★ same type
DLG2 p.Ala128Pro Uncertain significance ★ ⚠ 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/dlg2-p-ile897phe (accessed [today's date]).

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