Is AP3D1 p.Ser764= (c.2292C>T) pathogenic?

AP3D1 p.Ser764= (c.2292C>T) is classified Benign/Likely benign in AP3D1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Rare (popmax 0.196%, eas).

How common is AP3D1 p.Ser764= (c.2292C>T) in the general population?

AP3D1 p.Ser764= (c.2292C>T) is rare (popmax 0.196%, eas) (gnomAD).

AP3D1 p.Ser764=

c.2292C>T · rs376361242 · VCV761664

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.196%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -2.8
Overall
CADD	0.208	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.196% East Asian · 88/44,888 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.151%

Overall 0.0133% 214/1,613,386 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.196%	510
South Asian	0.0483%	2,070
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0144%	6,944
European (non-Finnish)	0.00585%	17,102
Admixed American	0.005%	20,009

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.Ser764=
Coding: c.2292C>T
MANE Select: NM_001261826
dbSNP: rs376361242
Type: single nucleotide variant
Location: chr19:2115276 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.45 · 6 PDB
Residue 764: the 'disordered' region; a modified residue (phosphoserine)

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-ser764 (accessed [today's date]).

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