Is AP3D1 p.Pro653Ser (c.1956_1957delinsCT) pathogenic?

AP3D1 p.Pro653Ser (c.19561957delinsCT) is classified Uncertain significance in AP3D1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-16). Absent from gnomAD.

How common is AP3D1 p.Pro653Ser (c.1956_1957delinsCT) in the general population?

AP3D1 p.Pro653Ser (c.1956_1957delinsCT) is absent from gnomAD (gnomAD).

AP3D1 p.Pro653Ser

c.1956_1957delinsCT · rs2145047371 · VCV1488548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.5	GERP -3.1
Regional constraint	o/e 1.04	unconstrained · MANE · 8,543 bp · p 0.28 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AP3D1
Protein: p.Pro653Ser
Coding: c.1956_1957delinsCT
MANE Select: NM_001261826
dbSNP: rs2145047371
Type: Indel
Location: chr19:2116649 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.45 · 6 PDB
Residue 653: the 'disordered' region

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

Similar variants

AP3D1 p.Pro653Thr Uncertain significance ★ ⚠ same residue
AP3D1 c.593-18_593-17delinsCG Benign/Likely benign ★★ same type
AP3D1 c.1860-15_1860-14delinsCT Uncertain significance ★ same type
AP3D1 c.193-12_193-11delinsAA Uncertain significance ★ same type
AP3D1 p.Ala53Thr Uncertain significance ★ same type
AP3D1 p.Arg640Ala 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-pro653ser (accessed [today's date]).

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