Is AP3D1 p.Pro703= (c.2109C>T) pathogenic?

AP3D1 p.Pro703= (c.2109C>T) is classified Benign/Likely benign in AP3D1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.72%, afr).

How common is AP3D1 p.Pro703= (c.2109C>T) in the general population?

AP3D1 p.Pro703= (c.2109C>T) is low-frequency (popmax 2.72%, afr) (gnomAD).

AP3D1 p.Pro703=

c.2109C>T · rs34286317 · VCV730352

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.72%, afr)

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 -6.3	GERP -2.8
Overall
CADD	0.113	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.72% African / African-American · 2,043/75,016 alleles

Filtering AF 2.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.59%

Overall 0.143% 2,311/1,613,198 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.72%	37
Admixed American	0.208%	480
Remaining individualsnot grpmax-eligible	0.146%	687
Middle Eastern	0.066%	1,516
South Asian	0.011%	9,109
East Asian	0.00446%	22,429
European (non-Finnish)	0.00305%	32,774

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.Pro703=
Coding: c.2109C>T
MANE Select: NM_001261826
dbSNP: rs34286317
Type: single nucleotide variant
Location: chr19:2115578 (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-pro703 (accessed [today's date]).

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