Is DLGAP2 p.Ala269Thr (c.805G>A) pathogenic?

DLGAP2 p.Ala269Thr (c.805G>A) is classified Uncertain significance in DLGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely benign (0.0658); Ultra-rare (popmax 0.0165%, mid).

How common is DLGAP2 p.Ala269Thr (c.805G>A) in the general population?

DLGAP2 p.Ala269Thr (c.805G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DLGAP2 p.Ala269Thr (c.805G>A)?

AlphaMissense predicts likely benign (score 0.0658) — an in-silico prediction, not a clinical call.

DLGAP2 p.Ala269Thr

c.805G>A · rs746322363 · VCV2232495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0658 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0658	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP 4.1, phastCons 0.074
Overall
CADD	12.24	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 A268T vs ClinVar A269T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000343% 5/1,457,850 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.00321%	31,186
Admixed American	0.00168%	59,594
African / African-American	0.00133%	75,008

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.Ala269Thr
Coding: c.805G>A
MANE Select: NM_001346810
dbSNP: rs746322363
Type: single nucleotide variant
Location: chr8:1549258 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 48.83
Residue 269: the 'disordered' region

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-ala269thr (accessed [today's date]).

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