Is DLG4 p.Phe684fs (c.2052del) pathogenic?

DLG4 p.Phe684fs (c.2052del) is classified Uncertain significance in DLG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). Associated with intellectual developmental disorder 62.

What condition is associated with DLG4 p.Phe684fs (c.2052del)?

DLG4 p.Phe684fs (c.2052del) is associated with intellectual developmental disorder 62 (ClinVar).

DLG4 p.Phe684fs

c.2052del · VCV4291759

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

intellectual developmental disorder 62

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (19 of 20, 16 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP -0.51, phastCons 1

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

Variant & gene context

Gene: DLG4
Protein: p.Phe684fs
Coding: c.2052del
MANE Select: NM_001321075
Type: Deletion
Location: chr17:7191283 (GRCh38)
Gene constraint: LOEUF 0.151 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.00 · 24 PDB
Residue 684: a UniProt-annotated variant site (in mrd62); the guanylate kinase-like domain

Full DLG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder 62 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLG4 p.Asn114fs Pathogenic ★★ same condition
DLG4 p.Glu572fs Pathogenic/Likely pathogenic ★★ same condition
DLG4 p.Gly109fs Pathogenic ★★ same condition
DLG4 p.Lys202fs Pathogenic ★★ same condition
DLG4 p.Phe340fs Pathogenic/Likely pathogenic ★★ same condition
DLG4 p.Phe487fs Pathogenic ★★ same condition
DLG4 p.Thr566fs Pathogenic ★★ same condition
DLG4 p.Val619fs Pathogenic ★★ 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/dlg4-p-phe684fs (accessed [today's date]).

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