Is DLGAP2 p.Glu892Gln (c.2674G>C) pathogenic?

DLGAP2 p.Glu892Gln (c.2674G>C) is classified Uncertain significance in DLGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-28). AlphaMissense: ambiguous (0.3964); Very rare (popmax 0.00236%, sas); Associated with DLGAP2-related disorder.

What condition is associated with DLGAP2 p.Glu892Gln (c.2674G>C)?

DLGAP2 p.Glu892Gln (c.2674G>C) is associated with DLGAP2-related disorder (ClinVar).

How common is DLGAP2 p.Glu892Gln (c.2674G>C) in the general population?

DLGAP2 p.Glu892Gln (c.2674G>C) is very rare (popmax 0.00236%, sas) (gnomAD).

What do computational predictors say about DLGAP2 p.Glu892Gln (c.2674G>C)?

AlphaMissense predicts ambiguous (score 0.3964) — an in-silico prediction, not a clinical call.

DLGAP2 p.Glu892Gln

c.2674G>C · rs2486197593 · VCV2632179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3964 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00236%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

DLGAP2-related disorder

Computational evidence

Protein change
AlphaMissense	0.3964	ambiguous
REVEL	0.698	pathogenic-leaning
SaProt	LLR -8.87	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E891Q vs ClinVar E892Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00236% South Asian · 2/84,666 alleles

Filtering AF 0.000392% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000147%

Overall 0.000142% 2/1,413,210 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: DLGAP2
Protein: p.Glu892Gln
Coding: c.2674G>C
MANE Select: NM_001346810
dbSNP: rs2486197593
Type: single nucleotide variant
Location: chr8:1678599 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 48.83

Full DLGAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DLGAP2-related disorder

Similar variants

DLGAP2 p.Asn662Thr Uncertain significance ⚠ same condition
DLGAP2 p.Leu192Val Uncertain significance ⚠ same condition
DLGAP2 p.Ser85Cys Uncertain significance ⚠ same condition
DLGAP2 c.107-10G>C Likely benign same condition
DLGAP2 c.1231-10C>G Likely benign same condition
DLGAP2 c.1810+10C>T Likely benign same condition
DLGAP2 c.2202+9C>T Likely benign same condition
DLGAP2 c.2949+5G>C Likely benign same condition

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/dlgap2-p-glu892gln (accessed [today's date]).

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