Is DLG3 p.Pro324Ser (c.970C>T) pathogenic?

DLG3 p.Pro324Ser (c.970C>T) is classified Uncertain significance in DLG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely pathogenic (0.619); Very rare (popmax 0.00876%, afr); Associated with Inborn genetic diseases.

What condition is associated with DLG3 p.Pro324Ser (c.970C>T)?

DLG3 p.Pro324Ser (c.970C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DLG3 p.Pro324Ser (c.970C>T) in the general population?

DLG3 p.Pro324Ser (c.970C>T) is very rare (popmax 0.00876%, afr) (gnomAD).

What do computational predictors say about DLG3 p.Pro324Ser (c.970C>T)?

AlphaMissense predicts likely pathogenic (score 0.619) — an in-silico prediction, not a clinical call.

DLG3 p.Pro324Ser

c.970C>T · rs375913970 · VCV2484470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.619 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00876%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.619	likely pathogenic
REVEL	0.395	indeterminate
SaProt	LLR -11.46	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 1,280 bp · p 0.96 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00876% African / African-American · 5/57,052 alleles

Filtering AF 0.00339% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00216%

Overall 0.00448% 5/111,704 alleles · very rare

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.Pro324Ser
Coding: c.970C>T
MANE Select: NM_021120
dbSNP: rs375913970
Type: single nucleotide variant
Location: chrX:70450768 (GRCh38)
Structure: AlphaFold pLDDT 74.35 · 3 PDB

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.Pro324Arg Uncertain significance ★ ⚠ same residue
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

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-pro324ser (accessed [today's date]).

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