Is DLGAP2 p.Gly718Arg (c.2152G>A) pathogenic?

DLGAP2 p.Gly718Arg (c.2152G>A) is classified Uncertain significance in DLGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: ambiguous (0.5364); Ultra-rare (popmax 0.0134%, amr).

How common is DLGAP2 p.Gly718Arg (c.2152G>A) in the general population?

DLGAP2 p.Gly718Arg (c.2152G>A) is ultra-rare (popmax 0.0134%, amr) (gnomAD).

What do computational predictors say about DLGAP2 p.Gly718Arg (c.2152G>A)?

AlphaMissense predicts ambiguous (score 0.5364) — an in-silico prediction, not a clinical call.

DLGAP2 p.Gly718Arg

c.2152G>A · rs1012436728 · VCV3082840

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5364 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5364	ambiguous
REVEL	0.673	pathogenic-leaning
SaProt	LLR -5.56	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 9.3	GERP 2.2, phastCons 1
Overall
CADD	28.7	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 G717R vs ClinVar G718R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% Admixed American · 7/52,046 alleles

Filtering AF 0.00627% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00448%

Overall 0.00174% 27/1,550,424 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0134%	7,435
African / African-American	0.00409%	24,423
Remaining individualsnot grpmax-eligible	0.00334%	29,950
European (non-Finnish)	0.00131%	76,408

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.Gly718Arg
Coding: c.2152G>A
MANE Select: NM_001346810
dbSNP: rs1012436728
Type: single nucleotide variant
Location: chr8:1668670 (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

Similar variants

DLGAP2 c.1810+14A>G Benign ★★ same type
DLGAP2 c.2160+19C>G Benign ★★ same type
DLGAP2 p.Glu678= Benign ★★ same type
DLGAP2 p.Pro464Gln Benign ★★ same type
DLGAP2 c.2203-7G>T Uncertain significance ★ same type
DLGAP2 p.Ala1019Gly Uncertain significance ★ ⚠ same type
DLGAP2 p.Ala1026Val Uncertain significance ★ ⚠ same type
DLGAP2 p.Ala116Thr 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/dlgap2-p-gly718arg (accessed [today's date]).

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