Is AP3D1 p.Gly129Ser (c.385G>A) pathogenic?

AP3D1 p.Gly129Ser (c.385G>A) is classified Uncertain significance in AP3D1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-04). AlphaMissense: ambiguous (0.5298); Very rare (popmax 8.5e-05%, nfe).

How common is AP3D1 p.Gly129Ser (c.385G>A) in the general population?

AP3D1 p.Gly129Ser (c.385G>A) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about AP3D1 p.Gly129Ser (c.385G>A)?

AlphaMissense predicts ambiguous (score 0.5298) — an in-silico prediction, not a clinical call.

AP3D1 p.Gly129Ser

c.385G>A · VCV4720782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5298 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5298	ambiguous
REVEL	0.436	indeterminate
SaProt	LLR -10.18	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 28 kb · p 3.4e-09 · regional, not allelic
Overall
CADD	25.5	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 8.5e-05% European (non-Finnish) · 1/1,176,980 alleles

Overall 0.000657% 1/152,234 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: AP3D1
Protein: p.Gly129Ser
Coding: c.385G>A
MANE Select: NM_001261826
Type: single nucleotide variant
Location: chr19:2132548 (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 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
AP3D1 p.Ala1213Thr Uncertain significance ★★ ⚠ same type
AP3D1 p.Ala247Val 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-gly129ser (accessed [today's date]).

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