Is AMH p.Arg129His (c.386G>A) pathogenic?

AMH p.Arg129His (c.386G>A) is classified Uncertain significance in AMH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-19). AlphaMissense: likely benign (0.0889); Ultra-rare (popmax 0.0179%, mid); Associated with Inborn genetic diseases.

What condition is associated with AMH p.Arg129His (c.386G>A)?

AMH p.Arg129His (c.386G>A) is associated with Inborn genetic diseases (ClinVar).

How common is AMH p.Arg129His (c.386G>A) in the general population?

AMH p.Arg129His (c.386G>A) is ultra-rare (popmax 0.0179%, mid) (gnomAD).

What do computational predictors say about AMH p.Arg129His (c.386G>A)?

AlphaMissense predicts likely benign (score 0.0889) — an in-silico prediction, not a clinical call.

AMH p.Arg129His

c.386G>A · VCV3535508

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0889 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0889	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -6.79	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 -1.3	GERP -1.6
Regional constraint	o/e 1.27	unconstrained · MANE · 2,621 bp · p 9.3e-15 · regional, not allelic
Overall
CADD	9.377	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 0.0179% Middle Eastern · 1/5,592 alleles

Filtering AF 0.00743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00526%

Overall 0.00139% 21/1,507,212 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0179%	5,592
East Asian	0.016%	6,243
African / African-American	0.00837%	11,951
Admixed American	0.0046%	21,741
European (non-Finnish)	0.000441%	226,725

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: AMH
Protein: p.Arg129His
Coding: c.386G>A
MANE Select: NM_000479
Type: single nucleotide variant
Location: chr19:2249718 (GRCh38)
Gene constraint: LOEUF 1.954 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.40 · 3 PDB
Residue 129: a disulfide bond

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AMH p.Arg129Cys Uncertain significance ★ ⚠ same residue
AMH p.Arg219His Uncertain significance ★★ ⚠ same condition
AMH p.Asp192Gly Uncertain significance ★★ ⚠ same condition
AMH p.Glu256Gln Uncertain significance ★★ ⚠ same condition
AMH p.Pro168Thr Uncertain significance ★★ ⚠ same condition
AMH p.Pro46His Uncertain significance ★★ ⚠ same condition
AMH p.Thr268Ala Uncertain significance ★★ ⚠ same condition
AMH p.Ala162Val Uncertain significance ★ ⚠ same condition

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/amh-p-arg129his (accessed [today's date]).

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