Is DLG4 p.Arg151Trp (c.451C>T) pathogenic?

DLG4 p.Arg151Trp (c.451C>T) is classified Uncertain significance in DLG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). AlphaMissense: ambiguous (0.4411); Very rare (popmax 8.48e-05%, nfe); Associated with intellectual developmental disorder 62.

What condition is associated with DLG4 p.Arg151Trp (c.451C>T)?

DLG4 p.Arg151Trp (c.451C>T) is associated with intellectual developmental disorder 62 (ClinVar).

How common is DLG4 p.Arg151Trp (c.451C>T) in the general population?

DLG4 p.Arg151Trp (c.451C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DLG4 p.Arg151Trp (c.451C>T)?

AlphaMissense predicts ambiguous (score 0.4411) — an in-silico prediction, not a clinical call.

DLG4 p.Arg151Trp

c.451C>T · rs2508024417 · VCV3254754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4411 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

intellectual developmental disorder 62

Computational evidence

Protein change
AlphaMissense	0.4411	ambiguous
REVEL	0.258	benign-leaning
SaProt	LLR -13.51	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 67 bp · p 0.31 · regional, not allelic
Overall
CADD	28.6	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,848 alleles

Overall 0.000137% 2/1,460,372 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	63,950
European (non-Finnish)grpmax	8.48e-05%	1,178,848

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DLG4
Protein: p.Arg151Trp
Coding: c.451C>T
MANE Select: NM_001321075
dbSNP: rs2508024417
Type: single nucleotide variant
Location: chr17:7203478 (GRCh38)
Gene constraint: LOEUF 0.151 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.00 · 24 PDB
Residue 151: the pdz 1 domain; a β-strand

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 c.1084-1G>T Pathogenic/Likely pathogenic ★★ same condition
DLG4 c.1478+2T>C Pathogenic/Likely pathogenic ★★ same condition
DLG4 c.1543+2T>C Pathogenic/Likely pathogenic ★★ same condition
DLG4 c.1592-1G>A Pathogenic/Likely pathogenic ★★ same condition
DLG4 c.1693+1G>A Pathogenic/Likely pathogenic ★★ same condition
DLG4 c.1866+2T>C Pathogenic/Likely pathogenic ★★ same condition
DLG4 c.210+1G>T Likely pathogenic ★★ same condition
DLG4 c.211-2A>G Pathogenic/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-arg151trp (accessed [today's date]).

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