Is DLG3 p.Arg217Ter (c.649C>T) pathogenic?

DLG3 p.Arg217Ter (c.649C>T) is classified Pathogenic in DLG3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-02). Absent from gnomAD v4.1; Associated with intellectual disability, X-linked 90.

What condition is associated with DLG3 p.Arg217Ter (c.649C>T)?

DLG3 p.Arg217Ter (c.649C>T) is associated with intellectual disability, X-linked 90 (ClinVar).

How common is DLG3 p.Arg217Ter (c.649C>T) in the general population?

DLG3 p.Arg217Ter (c.649C>T) is absent from gnomAD v4.1 (gnomAD).

DLG3 p.Arg217Ter

c.649C>T · VCV3393533

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

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 carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 1.9, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Arg217Ter
Coding: c.649C>T
MANE Select: NM_021120
Type: single nucleotide variant
Location: chrX:70449805 (GRCh38)
Structure: AlphaFold pLDDT 74.35 · 3 PDB
Residue 217: the pdz 1 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.Arg217Gln Uncertain significance ★★ ⚠ same residue
DLG3 p.Arg756Ter Pathogenic ★★ same condition
DLG3 p.Arg472His Uncertain significance ★★ ⚠ same condition
DLG3 p.Arg661Trp Uncertain significance ★★ ⚠ same condition
DLG3 p.Gly83Glu Uncertain significance ★★ ⚠ same condition
DLG3 p.His2Pro Uncertain significance ★★ ⚠ same condition
DLG3 p.Ile748Thr Uncertain significance ★★ ⚠ same condition
DLG3 p.Leu751His 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-arg217ter (accessed [today's date]).

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