Is AMBP p.His142Arg (c.425A>G) pathogenic?

AMBP p.His142Arg (c.425A>G) is classified Uncertain significance in AMBP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-26). AlphaMissense: likely benign (0.1193); Very rare (popmax 0.00267%, afr).

How common is AMBP p.His142Arg (c.425A>G) in the general population?

AMBP p.His142Arg (c.425A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about AMBP p.His142Arg (c.425A>G)?

AlphaMissense predicts likely benign (score 0.1193) — an in-silico prediction, not a clinical call.

AMBP p.His142Arg

c.425A>G · rs369188218 · VCV2230240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1193 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1193	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -4.57	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 1.8	GERP 1.6, phastCons 0.99
Regional constraint	o/e 1.06	unconstrained · MANE · 14 kb · p 0.33 · regional, not allelic
Overall
CADD	17.71	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 0.00267% African / African-American · 2/75,038 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,614,198 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,519
European (non-Finnish)	8.47e-05%	1,180,040

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.His142Arg
Coding: c.425A>G
MANE Select: NM_001633
dbSNP: rs369188218
Type: single nucleotide variant
Location: chr9:114074065 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.03 · 11 PDB
Residue 142: a disulfide bond; a β-strand

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

Similar variants

AMBP p.His142Asn 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-his142arg (accessed [today's date]).

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