Is AP3D1 p.Glu750Asp (c.2250G>C) pathogenic?

AP3D1 p.Glu750Asp (c.2250G>C) is classified Uncertain significance in AP3D1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-24). AlphaMissense: likely benign (0.0836); Ultra-rare (popmax 0.0307%, sas); Associated with Inborn genetic diseases.

What condition is associated with AP3D1 p.Glu750Asp (c.2250G>C)?

AP3D1 p.Glu750Asp (c.2250G>C) is associated with Inborn genetic diseases (ClinVar).

How common is AP3D1 p.Glu750Asp (c.2250G>C) in the general population?

AP3D1 p.Glu750Asp (c.2250G>C) is ultra-rare (popmax 0.0307%, sas) (gnomAD).

What do computational predictors say about AP3D1 p.Glu750Asp (c.2250G>C)?

AlphaMissense predicts likely benign (score 0.0836) — an in-silico prediction, not a clinical call.

AP3D1 p.Glu750Asp

c.2250G>C · rs778795157 · VCV1948179

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0836 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0836	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -7.17	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 -0.14	GERP 0.053
Regional constraint	o/e 1.04	unconstrained · MANE · 8,543 bp · p 0.28 · regional, not allelic
Overall
CADD	11.03	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% South Asian · 28/91,094 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00186% 30/1,611,624 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0307%	3,253
East Asian	0.00223%	44,894
Remaining individualsnot grpmax-eligible	0.0016%	62,448

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: AP3D1
Protein: p.Glu750Asp
Coding: c.2250G>C
MANE Select: NM_001261826
dbSNP: rs778795157
Type: single nucleotide variant
Location: chr19:2115318 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.45 · 6 PDB
Residue 750: the 'disordered' region

Full AP3D1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AP3D1 p.Glu750= Likely benign ★ same residue
AP3D1 c.856+3G>A Uncertain significance ★★ same condition
AP3D1 p.Ala1076Val Uncertain significance ★★ ⚠ same condition
AP3D1 p.Ala247Val Uncertain significance ★★ ⚠ same condition
AP3D1 p.Ala285Ser Uncertain significance ★★ ⚠ same condition
AP3D1 p.Ala299Thr Uncertain significance ★★ ⚠ same condition
AP3D1 p.Ala438Thr Uncertain significance ★★ ⚠ same condition
AP3D1 p.Ala450Thr Uncertain significance ★★ ⚠ 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/ap3d1-p-glu750asp (accessed [today's date]).

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