Is DLG2 p.Ala595Asp (c.1784C>A) pathogenic?

DLG2 p.Ala595Asp (c.1784C>A) is classified Uncertain significance in DLG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely pathogenic (0.9964); Very rare (popmax 0.0011%, sas).

How common is DLG2 p.Ala595Asp (c.1784C>A) in the general population?

DLG2 p.Ala595Asp (c.1784C>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DLG2 p.Ala595Asp (c.1784C>A)?

AlphaMissense predicts likely pathogenic (score 0.9964) — an in-silico prediction, not a clinical call.

DLG2 p.Ala595Asp

c.1784C>A · rs2549029417 · VCV3082771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9964 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9964	likely pathogenic
REVEL	0.509	indeterminate
SaProt	LLR -12.56	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 374 kb · p 4.3e-10 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A490D vs ClinVar A595D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,076 alleles

Overall 6.84e-05% 1/1,461,860 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: DLG2
Protein: p.Ala595Asp
Coding: c.1784C>A
MANE Select: NM_001142699
dbSNP: rs2549029417
Type: single nucleotide variant
Location: chr11:83786731 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 69.93 · 2 PDB
Residue 595: the sh3 domain

Full DLG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLG2 p.Arg797= Benign ★★ same type
DLG2 p.Gln944= Benign ★★ same type
DLG2 p.Leu459= Benign ★★ same type
DLG2 p.Leu514Pro Likely benign ★★ same type
DLG2 p.Lys59= Benign ★★ same type
DLG2 p.Ser804= Benign/Likely benign ★★ same type
DLG2 c.624+1G>A Uncertain significance ★ same type
DLG2 p.Ala128Pro Uncertain significance ★ ⚠ 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/dlg2-p-ala595asp (accessed [today's date]).

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