Is DLG4 p.Arg70Lys (c.209G>A) pathogenic?

DLG4 p.Arg70Lys (c.209G>A) is classified Uncertain significance in DLG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). AlphaMissense: likely pathogenic (0.9526); Absent from gnomAD v4.1; Associated with DLG4-related disorder.

What condition is associated with DLG4 p.Arg70Lys (c.209G>A)?

DLG4 p.Arg70Lys (c.209G>A) is associated with DLG4-related disorder (ClinVar).

How common is DLG4 p.Arg70Lys (c.209G>A) in the general population?

DLG4 p.Arg70Lys (c.209G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLG4 p.Arg70Lys (c.209G>A)?

AlphaMissense predicts likely pathogenic (score 0.9526) — an in-silico prediction, not a clinical call.

DLG4 p.Arg70Lys

c.209G>A · rs2508034347 · VCV2632746

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9526 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,354)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DLG4-related disorder

Computational evidence

Protein change
AlphaMissense	0.9526	likely pathogenic
REVEL	0.219	benign-leaning
SaProt	LLR -10.79	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 518 bp · p 6.9e-13 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,354). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DLG4
Protein: p.Arg70Lys
Coding: c.209G>A
MANE Select: NM_001321075
dbSNP: rs2508034347
Type: single nucleotide variant
Location: chr17:7204009 (GRCh38)
Gene constraint: LOEUF 0.151 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.00 · 24 PDB
Residue 70: the pdz 1 domain

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

Disease context

DLG4-related disorder

Similar variants

DLG4 c.1543+2T>C Pathogenic/Likely pathogenic ★★ same condition
DLG4 c.1693+1G>A Pathogenic/Likely pathogenic ★★ same condition
DLG4 p.Arg309Ter Pathogenic/Likely pathogenic ★★ same condition
DLG4 p.Arg516Ter Pathogenic ★★ same condition
DLG4 p.Arg586Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
DLG4 p.Arg617Ter Pathogenic ★★ same condition
DLG4 c.1515+1G>A Likely pathogenic ★ same condition
DLG4 c.1694-2A>G Likely 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-arg70lys (accessed [today's date]).

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