Is AP5B1 p.Arg252Pro (c.755G>C) pathogenic?

AP5B1 p.Arg252Pro (c.755G>C) is classified Uncertain significance in AP5B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-18). AlphaMissense: likely benign (0.0805); Absent from gnomAD v4.1.

How common is AP5B1 p.Arg252Pro (c.755G>C) in the general population?

AP5B1 p.Arg252Pro (c.755G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP5B1 p.Arg252Pro (c.755G>C)?

AlphaMissense predicts likely benign (score 0.0805) — an in-silico prediction, not a clinical call.

AP5B1 p.Arg252Pro

c.755G>C · rs541055336 · VCV2476553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0805 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0805	likely benign
SaProt	LLR -5.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3.1
Regional constraint	o/e 1.15	unconstrained · MANE · 2,732 bp · p 8.1e-07 · regional, not allelic
Overall
CADD	0.231	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: AP5B1
Protein: p.Arg252Pro
Coding: c.755G>C
MANE Select: NM_138368
dbSNP: rs541055336
Type: single nucleotide variant
Location: chr11:65779738 (GRCh38)
Gene constraint: LOEUF 1.424 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.29 · 2 PDB
Residue 252: the 'disordered' region

Full AP5B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP5B1 p.Arg731Ter Pathogenic/Likely pathogenic ★★ same type
AP5B1 p.Arg857Trp Uncertain significance ★★ ⚠ same type
AP5B1 p.Leu401Phe Uncertain significance ★★ ⚠ same type
AP5B1 p.Ala345= Likely benign ★★ same type
AP5B1 p.Arg155Ter Likely pathogenic ★ same type
AP5B1 p.Leu544Pro Likely pathogenic ★ same type
AP5B1 p.Ala192Val Uncertain significance ★ ⚠ same type
AP5B1 p.Ala239Val 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/ap5b1-p-arg252pro (accessed [today's date]).

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