Is AP3B2 p.Pro706His (c.2117C>A) pathogenic?

AP3B2 p.Pro706His (c.2117C>A) is classified Uncertain significance in AP3B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-24). AlphaMissense: ambiguous (0.3701); Absent from gnomAD v4.1.

How common is AP3B2 p.Pro706His (c.2117C>A) in the general population?

AP3B2 p.Pro706His (c.2117C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP3B2 p.Pro706His (c.2117C>A)?

AlphaMissense predicts ambiguous (score 0.3701) — an in-silico prediction, not a clinical call.

AP3B2 p.Pro706His

c.2117C>A · rs2548697933 · VCV1964098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3701 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,598,090)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3701	ambiguous
REVEL	0.258	benign-leaning
SaProt	LLR -5.82	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 5,925 bp · p 0.51 · regional, not allelic
Overall
CADD	27.6	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 P687H vs ClinVar P706H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,598,090). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AP3B2
Protein: p.Pro706His
Coding: c.2117C>A
MANE Select: NM_001278512
dbSNP: rs2548697933
Type: single nucleotide variant
Location: chr15:82664855 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 706: the 'disordered' region

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

Similar variants

AP3B2 p.Pro706= Likely benign ★ same residue
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

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-pro706his (accessed [today's date]).

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