Is DLG5 p.Arg563His (c.1688G>A) pathogenic?

DLG5 p.Arg563His (c.1688G>A) is classified Uncertain significance in DLG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely pathogenic (0.7589); Very rare (popmax 0.00333%, amr).

How common is DLG5 p.Arg563His (c.1688G>A) in the general population?

DLG5 p.Arg563His (c.1688G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DLG5 p.Arg563His (c.1688G>A)?

AlphaMissense predicts likely pathogenic (score 0.7589) — an in-silico prediction, not a clinical call.

DLG5 p.Arg563His

c.1688G>A · VCV3502337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7589 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7589	likely pathogenic
REVEL	0.489	indeterminate
SaProt	LLR -8.48	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 96 kb · p 1.7e-09 · regional, not allelic
Overall
CADD	28.8	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 0.00333% Admixed American · 2/59,984 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00056% 9/1,607,580 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,992
European (non-Finnish)	0.000593%	168,566

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.Arg563His
Coding: c.1688G>A
MANE Select: NM_004747
Type: single nucleotide variant
Location: chr10:77833974 (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.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-arg563his (accessed [today's date]).

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