Is DLG5 p.Ser866Phe (c.2597C>T) pathogenic?

DLG5 p.Ser866Phe (c.2597C>T) is classified Uncertain significance in DLG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.1272); Very rare (popmax 0.00167%, amr).

How common is DLG5 p.Ser866Phe (c.2597C>T) in the general population?

DLG5 p.Ser866Phe (c.2597C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DLG5 p.Ser866Phe (c.2597C>T)?

AlphaMissense predicts likely benign (score 0.1272) — an in-silico prediction, not a clinical call.

DLG5 p.Ser866Phe

c.2597C>T · VCV4012044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1272 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1272	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -8.46	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 7.5	phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 9,758 bp · p 0.78 · regional, not allelic
Overall
CADD	20.5	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 0.00167% Admixed American · 1/60,014 alleles

Overall 0.000124% 2/1,614,090 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,014
European (non-Finnish)	8.47e-05%	1,180,038

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.Ser866Phe
Coding: c.2597C>T
MANE Select: NM_004747
Type: single nucleotide variant
Location: chr10:77821887 (GRCh38)
Gene constraint: LOEUF 0.333 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.25 · 1 PDB
Residue 866: 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-ser866phe (accessed [today's date]).

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