Is AMBP p.His141Arg (c.422A>G) pathogenic?

AMBP p.His141Arg (c.422A>G) is classified Likely benign in AMBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely benign (0.0589); Very rare (popmax 0.00167%, amr).

How common is AMBP p.His141Arg (c.422A>G) in the general population?

AMBP p.His141Arg (c.422A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about AMBP p.His141Arg (c.422A>G)?

AlphaMissense predicts likely benign (score 0.0589) — an in-silico prediction, not a clinical call.

AMBP p.His141Arg

c.422A>G · rs769675878 · VCV2555531

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0589 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0589	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -4.38	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 -2.7	GERP -3
Regional constraint	o/e 1.06	unconstrained · MANE · 14 kb · p 0.33 · regional, not allelic
Overall
CADD	0.265	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 0.00167% Admixed American · 1/60,002 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,082 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
European (non-Finnish)	0.000254%	393,348

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.His141Arg
Coding: c.422A>G
MANE Select: NM_001633
dbSNP: rs769675878
Type: single nucleotide variant
Location: chr9:114074068 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.03 · 11 PDB
Residue 141: a disulfide bond; a β-strand

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

Similar variants

AMBP p.His141Tyr 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-his141arg (accessed [today's date]).

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