Is AP3B1 p.Ser686Pro (c.2056T>C) pathogenic?

AP3B1 p.Ser686Pro (c.2056T>C) is classified Uncertain significance in AP3B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-29). AlphaMissense: likely benign (0.1048); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AP3B1 p.Ser686Pro (c.2056T>C)?

AP3B1 p.Ser686Pro (c.2056T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AP3B1 p.Ser686Pro (c.2056T>C) in the general population?

AP3B1 p.Ser686Pro (c.2056T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP3B1 p.Ser686Pro (c.2056T>C)?

AlphaMissense predicts likely benign (score 0.1048) — an in-silico prediction, not a clinical call.

AP3B1 p.Ser686Pro

c.2056T>C · rs2530967513 · VCV2314537

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1048 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1048	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -11.18	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 213 kb · p 0.0039 · regional, not allelic
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AP3B1
Protein: p.Ser686Pro
Coding: c.2056T>C
MANE Select: NM_003664
dbSNP: rs2530967513
Type: single nucleotide variant
Location: chr5:78116147 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.85 · 5 PDB
Residue 686: the 'disordered' region

Full AP3B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AP3B1 p.Ala643Val Uncertain significance ★★ ⚠ same condition
AP3B1 p.Ala844Val Uncertain significance ★★ ⚠ same condition
AP3B1 p.Arg227His Uncertain significance ★★ ⚠ same condition
AP3B1 p.Arg509Gln Uncertain significance ★★ ⚠ same condition
AP3B1 p.Arg649Gln Uncertain significance ★★ ⚠ same condition
AP3B1 p.Arg730Gln Uncertain significance ★★ ⚠ same condition
AP3B1 p.Asp285Gly Uncertain significance ★★ ⚠ same condition
AP3B1 p.Asp488Asn Uncertain significance ★★ ⚠ same condition

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/ap3b1-p-ser686pro (accessed [today's date]).

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