Is AP3D1 p.Asp41Glu (c.123T>G) pathogenic?

AP3D1 p.Asp41Glu (c.123T>G) is classified Uncertain significance in AP3D1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-23). AlphaMissense: ambiguous (0.3952); Very rare (popmax 8.48e-05%, nfe).

How common is AP3D1 p.Asp41Glu (c.123T>G) in the general population?

AP3D1 p.Asp41Glu (c.123T>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about AP3D1 p.Asp41Glu (c.123T>G)?

AlphaMissense predicts ambiguous (score 0.3952) — an in-silico prediction, not a clinical call.

AP3D1 p.Asp41Glu

c.123T>G · VCV4718243

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3952 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3952	ambiguous
REVEL	0.091	moderately benign-leaning
SaProt	LLR -5.30	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.9	GERP -2.9
Regional constraint	o/e 0.71	unconstrained · MANE · 28 kb · p 3.4e-09 · regional, not allelic
Overall
CADD	17.13	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 8.48e-05% European (non-Finnish) · 1/1,179,936 alleles

Overall 6.84e-05% 1/1,461,392 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.Asp41Glu
Coding: c.123T>G
MANE Select: NM_001261826
Type: single nucleotide variant
Location: chr19:2138688 (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.Asp41Gly 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
AP3D1 p.Ala1213Thr 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-asp41glu (accessed [today's date]).

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