Is DLG5 p.Pro825Leu (c.2474C>T) pathogenic?

DLG5 p.Pro825Leu (c.2474C>T) is classified Uncertain significance in DLG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-18). AlphaMissense: likely benign (0.0736); Ultra-rare (popmax 0.024%, afr).

How common is DLG5 p.Pro825Leu (c.2474C>T) in the general population?

DLG5 p.Pro825Leu (c.2474C>T) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about DLG5 p.Pro825Leu (c.2474C>T)?

AlphaMissense predicts likely benign (score 0.0736) — an in-silico prediction, not a clinical call.

DLG5 p.Pro825Leu

c.2474C>T · rs376750224 · VCV2263565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0736 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0736	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -5.93	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	phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 9,758 bp · p 0.78 · regional, not allelic
Overall
CADD	17.43	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.024% African / African-American · 18/75,038 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00496% 80/1,614,174 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,169
East Asian	0.0134%	7,480
South Asian	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)	0.00398%	25,107
Finnishnot grpmax-eligible	0.00156%	64,024

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: DLG5
Protein: p.Pro825Leu
Coding: c.2474C>T
MANE Select: NM_004747
dbSNP: rs376750224
Type: single nucleotide variant
Location: chr10:77822010 (GRCh38)
Gene constraint: LOEUF 0.333 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.25 · 1 PDB
Residue 825: a UniProt-annotated variant site (in yuvob; likely pathogenic; fails to fully rescue abnormal pronephros development and ventriculomegaly when expressed in dlg5-null xenopus embryos)

Full DLG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLG5 p.Arg166Cys Uncertain significance ★★ ⚠ same type
DLG5 p.Leu1192Pro Uncertain significance ★★ ⚠ same type
DLG5 c.1622+8G>A Benign ★★ same type
DLG5 c.3672-5C>T Benign/Likely benign ★★ same type
DLG5 p.Ala1447= Benign ★★ same type
DLG5 p.Ala1600Val Benign ★★ same type
DLG5 p.Ala1738Thr Benign ★★ same type
DLG5 p.Ala741= Benign/Likely benign ★★ same type

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/dlg5-p-pro825leu (accessed [today's date]).

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