Is AP3B2 p.Ser718Arg (c.2154T>A) pathogenic?

AP3B2 p.Ser718Arg (c.2154T>A) is classified Uncertain significance in AP3B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). AlphaMissense: ambiguous (0.4108); Absent from gnomAD v4.1.

How common is AP3B2 p.Ser718Arg (c.2154T>A) in the general population?

AP3B2 p.Ser718Arg (c.2154T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP3B2 p.Ser718Arg (c.2154T>A)?

AlphaMissense predicts ambiguous (score 0.4108) — an in-silico prediction, not a clinical call.

AP3B2 p.Ser718Arg

c.2154T>A · rs183833442 · VCV2093878

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4108 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4108	ambiguous
REVEL	0.206	benign-leaning
SaProt	LLR -11.36	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -3.1
Regional constraint	o/e 1.03	unconstrained · MANE · 5,925 bp · p 0.51 · regional, not allelic
Overall
CADD	6.883	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S699R vs ClinVar S718R) — verify the residue.

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: AP3B2
Protein: p.Ser718Arg
Coding: c.2154T>A
MANE Select: NM_001278512
dbSNP: rs183833442
Type: single nucleotide variant
Location: chr15:82664474 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 718: the 'disordered' region

Full AP3B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP3B2 c.114-1G>A Likely pathogenic ★★ same type
AP3B2 p.Arg977Ter Pathogenic ★★ same type
AP3B2 p.Gln839Ter Pathogenic/Likely pathogenic ★★ same type
AP3B2 c.1110+3G>C Uncertain significance ★★ same type
AP3B2 c.1853-5C>A Uncertain significance ★★ same type
AP3B2 c.2834-3C>A Uncertain significance ★★ same type
AP3B2 p.Ala1076Pro Uncertain significance ★★ same type
AP3B2 p.Ala1098Asp 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/ap3b2-p-ser718arg (accessed [today's date]).

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