Is DLG3 p.Ala463Val (c.1388C>T) pathogenic?

DLG3 p.Ala463Val (c.1388C>T) is classified Likely benign in DLG3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-01). AlphaMissense: likely pathogenic (0.8431); Ultra-rare (popmax 0.0368%, afr); Associated with Inborn genetic diseases.

What condition is associated with DLG3 p.Ala463Val (c.1388C>T)?

DLG3 p.Ala463Val (c.1388C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DLG3 p.Ala463Val (c.1388C>T) in the general population?

DLG3 p.Ala463Val (c.1388C>T) is ultra-rare (popmax 0.0368%, afr) (gnomAD).

What do computational predictors say about DLG3 p.Ala463Val (c.1388C>T)?

AlphaMissense predicts likely pathogenic (score 0.8431) — an in-silico prediction, not a clinical call.

DLG3 p.Ala463Val

c.1388C>T · rs371545673 · VCV210849

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8431 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0368%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8431	likely pathogenic
REVEL	0.243	benign-leaning
SaProt	LLR -12.01	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 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 25 kb · p 0.38 · regional, not allelic
Overall
CADD	25.7	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 0.0368% African / African-American · 21/57,083 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0207%

Overall 0.00232% 28/1,207,737 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0368%	2,718
Admixed American	0.00875%	11,434
European (non-Finnish)	0.000336%	297,804

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: DLG3
Protein: p.Ala463Val
Coding: c.1388C>T
MANE Select: NM_021120
dbSNP: rs371545673
Type: single nucleotide variant
Location: chrX:70454299 (GRCh38)
Structure: AlphaFold pLDDT 74.35 · 3 PDB
Residue 463: the pdz 3 domain; a β-strand

Full DLG3 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

DLG3 p.Arg211Ter Pathogenic ★★ same condition
DLG3 p.Arg217Gln Uncertain significance ★★ ⚠ same condition
DLG3 p.Arg271Cys Uncertain significance ★★ ⚠ same condition
DLG3 p.Arg497Gln Uncertain significance ★★ ⚠ same condition
DLG3 p.Arg710Gln Uncertain significance ★★ ⚠ same condition
DLG3 p.Asp599Asn Uncertain significance ★★ ⚠ same condition
DLG3 p.Glu222Lys Uncertain significance ★★ ⚠ same condition
DLG3 p.His2Pro 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-ala463val (accessed [today's date]).

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