Is DLGAP2 p.Met1024Thr (c.3071T>C) pathogenic?

DLGAP2 p.Met1024Thr (c.3071T>C) is classified Uncertain significance in DLGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-24). AlphaMissense: ambiguous (0.4629); Very rare (popmax 0.00135%, afr).

How common is DLGAP2 p.Met1024Thr (c.3071T>C) in the general population?

DLGAP2 p.Met1024Thr (c.3071T>C) is very rare (popmax 0.00135%, afr) (gnomAD).

What do computational predictors say about DLGAP2 p.Met1024Thr (c.3071T>C)?

AlphaMissense predicts ambiguous (score 0.4629) — an in-silico prediction, not a clinical call.

DLGAP2 p.Met1024Thr

c.3071T>C · VCV3840355

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4629 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Computational evidence

Protein change
AlphaMissense	0.4629	ambiguous
REVEL	0.624	indeterminate
SaProt	LLR -12.47	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.2, phastCons 1
Overall
CADD	23.3	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 M1023T vs ClinVar M1024T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00135% African / African-American · 1/74,344 alleles

Overall 6.97e-05% 1/1,434,818 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.Met1024Thr
Coding: c.3071T>C
MANE Select: NM_001346810
Type: single nucleotide variant
Location: chr8:1701309 (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-met1024thr (accessed [today's date]).

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