Is DLG5 p.Arg256Trp (c.766C>T) pathogenic?

DLG5 p.Arg256Trp (c.766C>T) is classified Uncertain significance in DLG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.1847); Very rare (popmax 8.48e-05%, nfe).

How common is DLG5 p.Arg256Trp (c.766C>T) in the general population?

DLG5 p.Arg256Trp (c.766C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DLG5 p.Arg256Trp (c.766C>T)?

AlphaMissense predicts likely benign (score 0.1847) — an in-silico prediction, not a clinical call.

DLG5 p.Arg256Trp

c.766C>T · VCV4241087

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1847 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1847	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -10.91	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
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 0.79	unconstrained · MANE · 96 kb · p 1.7e-09 · regional, not allelic
Overall
CADD	25.2	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 8.48e-05% European (non-Finnish) · 1/1,178,704 alleles

Overall 6.86e-05% 1/1,458,728 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: DLG5
Protein: p.Arg256Trp
Coding: c.766C>T
MANE Select: NM_004747
Type: single nucleotide variant
Location: chr10:77853452 (GRCh38)
Gene constraint: LOEUF 0.333 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.25 · 1 PDB

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

Similar variants

DLG5 p.Arg256Gln Uncertain significance ★ ⚠ same residue
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

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-arg256trp (accessed [today's date]).

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