Is AMH p.Leu112fs (c.333del) pathogenic?

AMH p.Leu112fs (c.333del) is classified Likely pathogenic in AMH (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-29). Very rare (popmax 8.81e-05%, nfe); Associated with AMH-related disorder.

What condition is associated with AMH p.Leu112fs (c.333del)?

AMH p.Leu112fs (c.333del) is associated with AMH-related disorder (ClinVar).

How common is AMH p.Leu112fs (c.333del) in the general population?

AMH p.Leu112fs (c.333del) is very rare (popmax 8.81e-05%, nfe) (gnomAD).

AMH p.Leu112fs

c.333del · VCV4939822

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.81e-05%, nfe)

Conditions

AMH-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.49	GERP -1.6

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.81e-05% European (non-Finnish) · 1/1,134,936 alleles

Overall 7.35e-05% 1/1,361,318 alleles · very rare

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.Leu112fs
Coding: c.333del
MANE Select: NM_000479
Type: Deletion
Location: chr19:2249664 (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 112: a disulfide bond

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

Disease context

AMH-related disorder

Similar variants

AMH p.Gln217Ter Pathogenic/Likely pathogenic ★★ same condition
AMH p.Pro304Thr Uncertain significance ★★ ⚠ same condition
AMH p.Val12Gly Uncertain significance ★★ ⚠ same condition
AMH p.Arg302Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
AMH p.His506Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
AMH p.Pro352Leu Uncertain significance ★ ⚠ same condition
AMH c.665-7A>G Likely benign same condition
AMH c.-2C>T Likely benign 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-leu112fs (accessed [today's date]).

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