Is AP5Z1 p.Arg266Ser (c.798G>C) pathogenic?

AP5Z1 p.Arg266Ser (c.798G>C) is classified Uncertain significance in AP5Z1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: likely benign (0.2044); Absent from gnomAD v4.1.

How common is AP5Z1 p.Arg266Ser (c.798G>C) in the general population?

AP5Z1 p.Arg266Ser (c.798G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP5Z1 p.Arg266Ser (c.798G>C)?

AlphaMissense predicts likely benign (score 0.2044) — an in-silico prediction, not a clinical call.

AP5Z1 p.Arg266Ser

c.798G>C · rs2534047486 · VCV2571274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2044 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2044	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.31	acceptor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.5	GERP -0.94, phastCons 0.84
Regional constraint	o/e 1.43	unconstrained · MANE · 16 kb · p 5.7e-46 · regional, not allelic
Overall
CADD	17.51	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: AP5Z1
Protein: p.Arg266Ser
Coding: c.798G>C
MANE Select: NM_014855
dbSNP: rs2534047486
Type: single nucleotide variant
Location: chr7:4784915 (GRCh38)
Gene constraint: LOEUF 1.641 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.32

Full AP5Z1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP5Z1 c.1312-2A>G Pathogenic/Likely pathogenic ★★ same type
AP5Z1 c.1707+1G>A Likely pathogenic ★★ same type
AP5Z1 c.1806-1G>C Likely pathogenic ★★ same type
AP5Z1 p.Arg138Ter Pathogenic/Likely pathogenic ★★ same type
AP5Z1 p.Arg310Ter Pathogenic/Likely pathogenic ★★ same type
AP5Z1 p.Arg311Ter Pathogenic/Likely pathogenic ★★ same type
AP5Z1 p.Arg345Ter Pathogenic/Likely pathogenic ★★ same type
AP5Z1 p.Gln17Ter Pathogenic/Likely pathogenic ★★ 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/ap5z1-p-arg266ser (accessed [today's date]).

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