Is AMBP p.Arg293Gln (c.878G>A) pathogenic?

AMBP p.Arg293Gln (c.878G>A) is classified Uncertain significance in AMBP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely benign (0.0745); Ultra-rare (popmax 0.0329%, mid).

How common is AMBP p.Arg293Gln (c.878G>A) in the general population?

AMBP p.Arg293Gln (c.878G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about AMBP p.Arg293Gln (c.878G>A)?

AlphaMissense predicts likely benign (score 0.0745) — an in-silico prediction, not a clinical call.

AMBP p.Arg293Gln

c.878G>A · VCV3534674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0745 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0745	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -6.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.6	GERP -4.9
Regional constraint	o/e 1.06	unconstrained · MANE · 14 kb · p 0.33 · regional, not allelic
Overall
CADD	0.03	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

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00297% 48/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
South Asian	0.00659%	15,179
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.00297%	33,715
Admixed American	0.00167%	59,986
African / African-American	0.00133%	74,948

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.Arg293Gln
Coding: c.878G>A
MANE Select: NM_001633
Type: single nucleotide variant
Location: chr9:114061074 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.03 · 11 PDB
Residue 293: a disulfide bond; the bpti/kunitz inhibitor 2 domain

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

Similar variants

AMBP p.Arg293Trp Uncertain significance ★ ⚠ same residue
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

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-arg293gln (accessed [today's date]).

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