Is AMBP p.Arg282Gln (c.845G>A) pathogenic?

AMBP p.Arg282Gln (c.845G>A) is classified Uncertain significance in AMBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely pathogenic (0.6249); Very rare (popmax 0.00822%, nfe).

How common is AMBP p.Arg282Gln (c.845G>A) in the general population?

AMBP p.Arg282Gln (c.845G>A) is very rare (popmax 0.00822%, nfe) (gnomAD).

What do computational predictors say about AMBP p.Arg282Gln (c.845G>A)?

AlphaMissense predicts likely pathogenic (score 0.6249) — an in-silico prediction, not a clinical call.

AMBP p.Arg282Gln

c.845G>A · VCV4090432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6249 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00822%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6249	likely pathogenic
REVEL	0.289	benign-leaning
SaProt	LLR -11.84	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 14 kb · p 0.33 · regional, not allelic
Overall
CADD	29.3	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

Grpmax group 0.00822% European (non-Finnish) · 97/1,180,032 alleles

Filtering AF 0.00689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00657% 106/1,614,000 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00822%	12,165
African / African-American	0.00667%	14,990
Admixed American	0.00333%	30,001
Remaining individualsnot grpmax-eligible	0.0032%	31,243

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AMBP
Protein: p.Arg282Gln
Coding: c.845G>A
MANE Select: NM_001633
Type: single nucleotide variant
Location: chr9:114061432 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.03 · 11 PDB

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

Similar variants

AMBP p.Ala13Thr Uncertain significance ★ ⚠ same type
AMBP p.Ala19Val Uncertain significance ★ ⚠ same type
AMBP p.Ala255Thr Uncertain significance ★ ⚠ same type
AMBP p.Ala285Val Uncertain significance ★ ⚠ same type
AMBP p.Ala304Thr Uncertain significance ★ ⚠ same type
AMBP p.Ala48Thr Uncertain significance ★ ⚠ same type
AMBP p.Ala74Thr Uncertain significance ★ ⚠ same type
AMBP p.Arg185Gln 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/ambp-p-arg282gln (accessed [today's date]).

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