Is DLG5 p.Ala1493Pro (c.4477G>C) pathogenic?

DLG5 p.Ala1493Pro (c.4477G>C) is classified Uncertain significance in DLG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: likely benign (0.0831); Very rare (popmax 0.0067%, nfe).

How common is DLG5 p.Ala1493Pro (c.4477G>C) in the general population?

DLG5 p.Ala1493Pro (c.4477G>C) is very rare (popmax 0.0067%, nfe) (gnomAD).

What do computational predictors say about DLG5 p.Ala1493Pro (c.4477G>C)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

DLG5 p.Ala1493Pro

c.4477G>C · rs138734012 · VCV2366809

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.34	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 -1.9
Regional constraint	o/e 0.89	unconstrained · MANE · 20 kb · p 0.0056 · regional, not allelic
Overall
CADD	0.31	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 0.0067% European (non-Finnish) · 79/1,179,470 alleles

Filtering AF 0.00547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00506%

Overall 0.00496% 80/1,612,404 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0067%	14,930
Remaining individualsnot grpmax-eligible	0.0016%	62,392

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.Ala1493Pro
Coding: c.4477G>C
MANE Select: NM_004747
dbSNP: rs138734012
Type: single nucleotide variant
Location: chr10:77809717 (GRCh38)
Gene constraint: LOEUF 0.333 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.25 · 1 PDB
Residue 1493: the 'disordered' region; 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-ala1493pro (accessed [today's date]).

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