Is AMBP p.Arg39Gln (c.116G>A) pathogenic?

AMBP p.Arg39Gln (c.116G>A) is classified Uncertain significance in AMBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.0787); Very rare (popmax 0.00329%, sas).

How common is AMBP p.Arg39Gln (c.116G>A) in the general population?

AMBP p.Arg39Gln (c.116G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about AMBP p.Arg39Gln (c.116G>A)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

AMBP p.Arg39Gln

c.116G>A · rs535072502 · VCV2557361

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.456	indeterminate
SaProt	LLR -4.96	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.2, phastCons 0.96
Regional constraint	o/e 1.07	unconstrained · MANE · 4,101 bp · p 0.37 · regional, not allelic
Overall
CADD	21.4	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 0.00329% South Asian · 3/91,074 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000682% 11/1,614,052 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,358
African / African-American	0.00266%	37,533
East Asian	0.00223%	44,880
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.000339%	295,007

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.Arg39Gln
Coding: c.116G>A
MANE Select: NM_001633
dbSNP: rs535072502
Type: single nucleotide variant
Location: chr9:114078094 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.03 · 11 PDB
Residue 39: an α-helix

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-arg39gln (accessed [today's date]).

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