Is DLG4 p.Ala249Ser (c.745G>T) pathogenic?

DLG4 p.Ala249Ser (c.745G>T) is classified Likely benign in DLG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely benign (0.0748); Ultra-rare (popmax 0.04%, afr); Associated with Inborn genetic diseases.

What condition is associated with DLG4 p.Ala249Ser (c.745G>T)?

DLG4 p.Ala249Ser (c.745G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DLG4 p.Ala249Ser (c.745G>T) in the general population?

DLG4 p.Ala249Ser (c.745G>T) is ultra-rare (popmax 0.04%, afr) (gnomAD).

What do computational predictors say about DLG4 p.Ala249Ser (c.745G>T)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

DLG4 p.Ala249Ser

c.745G>T · VCV3840308

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -1.5, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 13 kb · p 1.2e-30 · regional, not allelic
Overall
CADD	23.2	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

Grpmax group 0.04% African / African-American · 30/74,926 alleles

Filtering AF 0.0288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00192% 31/1,613,894 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.04%	2,498
Remaining individualsnot grpmax-eligible	0.0016%	62,464

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.Ala249Ser
Coding: c.745G>T
MANE Select: NM_001321075
Type: single nucleotide variant
Location: chr17:7202945 (GRCh38)
Gene constraint: LOEUF 0.151 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.00 · 24 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLG4 p.Arg313Ter Pathogenic ★★ same condition
DLG4 p.Glu65Ter Pathogenic ★★ same condition
DLG4 p.Arg455Cys Uncertain significance ★★ ⚠ same condition
DLG4 p.Glu160Asp Uncertain significance ★★ ⚠ same condition
DLG4 p.Tyr533Cys Uncertain significance ★★ ⚠ same condition
DLG4 p.Thr57Ile Likely benign ★★ ⚠ same condition
DLG4 p.Val297Ala Likely benign ★★ ⚠ same condition
DLG4 c.335+1G>A 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-ala249ser (accessed [today's date]).

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