Is AP3D1 c.273+231T>C pathogenic?

AP3D1 c.273+231T>C is classified Benign in AP3D1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-10). Common (popmax 42.9%, nfe) — too common for a highly-penetrant pathogenic allele.

AP3D1 c.273+231T>C

Q: How common is AP3D1 c.273+231T>C in the general population?

AP3D1 c.273+231T>C is common (popmax 42.9%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs2018890 · VCV1266586

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 42.9%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
Splice region	donor +231	deep intronic (+231 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Non-coding constraint	Z 3.23	1 kb window · o/e 0.80 · regional · uncalibrated
Overall
CADD	5.138	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.9% European (non-Finnish) · 29,121/67,934 alleles

Filtering AF 42.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.3%

Overall 32.2% 48,932/151,818 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	46.1%	2
European (non-Finnish)grpmax	42.9%	2
Ashkenazi Jewishnot grpmax-eligible	41.9%	2
Finnishnot grpmax-eligible	37.6%	3
Middle Eastern	37.1%	3
Remaining individualsnot grpmax-eligible	34.4%	3
Admixed American	31.5%	3
South Asian	20.5%	5
East Asian	20.5%	5
African / African-American	15.3%	7

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.273+231T>C
MANE Select: NM_001261826
dbSNP: rs2018890
Type: single nucleotide variant
Location: chr19:2137496 (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-c-273-plus-231t-c (accessed [today's date]).

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