Is DLG3 p.Ala280= (c.840G>A) pathogenic?

DLG3 p.Ala280= (c.840G>A) is classified Uncertain significance in DLG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). Absent from gnomAD v4.1; Associated with intellectual disability, X-linked 90.

What condition is associated with DLG3 p.Ala280= (c.840G>A)?

DLG3 p.Ala280= (c.840G>A) is associated with intellectual disability, X-linked 90 (ClinVar).

How common is DLG3 p.Ala280= (c.840G>A) in the general population?

DLG3 p.Ala280= (c.840G>A) is absent from gnomAD v4.1 (gnomAD).

DLG3 p.Ala280=

c.840G>A · VCV3901953

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual disability, X-linked 90

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.75	donor loss · deltas
Pangolin	Δ0.73	loss · gain 0.64 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

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: DLG3
Protein: p.Ala280=
Coding: c.840G>A
MANE Select: NM_021120
Type: single nucleotide variant
Location: chrX:70450305 (GRCh38)
Structure: AlphaFold pLDDT 74.35 · 3 PDB
Residue 280: the pdz 2 domain; a β-strand

Full DLG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, X-linked 90 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLG3 p.Ala280Gly Uncertain significance ★ ⚠ same residue
DLG3 p.Ala280Val Uncertain significance ★ ⚠ same residue
DLG3 p.Arg217Ter Pathogenic ★★ same condition
DLG3 p.Arg756Ter Pathogenic ★★ same condition
DLG3 p.Arg217Gln Uncertain significance ★★ ⚠ same condition
DLG3 p.Arg472His Uncertain significance ★★ ⚠ same condition
DLG3 p.Arg661Trp Uncertain significance ★★ ⚠ same condition
DLG3 p.Gly83Glu 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/dlg3-p-ala280 (accessed [today's date]).

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