Is DLG5 p.Asp729Glu (c.2187C>A) pathogenic?

DLG5 p.Asp729Glu (c.2187C>A) is classified Uncertain significance in DLG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.1599); Absent from gnomAD v4.1.

How common is DLG5 p.Asp729Glu (c.2187C>A) in the general population?

DLG5 p.Asp729Glu (c.2187C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLG5 p.Asp729Glu (c.2187C>A)?

AlphaMissense predicts likely benign (score 0.1599) — an in-silico prediction, not a clinical call.

DLG5 p.Asp729Glu

c.2187C>A · VCV4660369

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1599 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,512)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1599	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.52	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 2.8	phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 8,247 bp · p 2.1e-13 · regional, not allelic
Overall
CADD	17.95	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

No allele count reported in gnomAD v4.1 (AN 1,613,512). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DLG5
Protein: p.Asp729Glu
Coding: c.2187C>A
MANE Select: NM_004747
Type: single nucleotide variant
Location: chr10:77828984 (GRCh38)
Gene constraint: LOEUF 0.333 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.25 · 1 PDB
Residue 729: the pdz 2 domain

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-asp729glu (accessed [today's date]).

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