Is AP3D1 p.His495Asp (c.1483C>G) pathogenic?

AP3D1 p.His495Asp (c.1483C>G) is classified Uncertain significance in AP3D1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-05). AlphaMissense: ambiguous (0.436); Ultra-rare (popmax 0.0117%, amr).

How common is AP3D1 p.His495Asp (c.1483C>G) in the general population?

AP3D1 p.His495Asp (c.1483C>G) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about AP3D1 p.His495Asp (c.1483C>G)?

AlphaMissense predicts ambiguous (score 0.436) — an in-silico prediction, not a clinical call.

AP3D1 p.His495Asp

c.1483C>G · rs766047908 · VCV2983565

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.436 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Computational evidence

Protein change
AlphaMissense	0.436	ambiguous
REVEL	0.401	indeterminate
SaProt	LLR -5.37	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,612 bp · p 7.4e-05 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,926 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000434% 7/1,612,528 alleles · ultra-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: AP3D1
Protein: p.His495Asp
Coding: c.1483C>G
MANE Select: NM_001261826
dbSNP: rs766047908
Type: single nucleotide variant
Location: chr19:2118831 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.45 · 6 PDB

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

Similar variants

AP3D1 p.His495Tyr Uncertain significance ★★ ⚠ same residue
AP3D1 p.His495Arg Uncertain significance ★ ⚠ same residue
AP3D1 c.2001+6C>T Uncertain significance ★★ same type
AP3D1 c.2601+6G>T Uncertain significance ★★ same type
AP3D1 c.856+3G>A Uncertain significance ★★ same type
AP3D1 p.Ala1076Val Uncertain significance ★★ ⚠ same type
AP3D1 p.Ala1093Val Uncertain significance ★★ ⚠ same type
AP3D1 p.Ala1148Val 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/ap3d1-p-his495asp (accessed [today's date]).

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