Is AMH p.Arg40Ter (c.118C>T) pathogenic?

AMH p.Arg40Ter (c.118C>T) is classified Pathogenic/Likely pathogenic in AMH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-21). Very rare (popmax 0.00401%, afr); Associated with persistent Mullerian duct syndrome.

What condition is associated with AMH p.Arg40Ter (c.118C>T)?

AMH p.Arg40Ter (c.118C>T) is associated with persistent Mullerian duct syndrome (ClinVar).

How common is AMH p.Arg40Ter (c.118C>T) in the general population?

AMH p.Arg40Ter (c.118C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

AMH p.Arg40Ter

c.118C>T · VCV3583552

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

persistent Mullerian duct syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 5
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.8	GERP -1.6
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,742 alleles

Filtering AF 0.00115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000973%

Overall 0.00193% 31/1,604,862 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00805%	12,421
African / African-Americangrpmax	0.00401%	24,914
European (non-Finnish)	0.00178%	56,027
Finnishnot grpmax-eligible	0.00162%	61,708
South Asian	0.00112%	89,662

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg40Ter
Coding: c.118C>T
MANE Select: NM_000479
Type: single nucleotide variant
Location: chr19:2249450 (GRCh38)
Gene constraint: LOEUF 1.954 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.40 · 3 PDB

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

Disease context

persistent Mullerian duct syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AMH p.Gln217Ter Pathogenic/Likely pathogenic ★★ same condition
AMH p.Glu389Ter Pathogenic/Likely pathogenic ★★ same condition
AMH p.Gly101Arg Likely pathogenic ★★ same condition
AMH p.Pro151Ser Pathogenic ★★ ⚠ same condition
AMH p.Pro398Leu Uncertain significance ★★ ⚠ same condition
AMH p.Thr268Ala Uncertain significance ★★ ⚠ same condition
AMH p.Thr99Ser Uncertain significance ★★ ⚠ same condition
AMH p.Ala86= Benign/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-arg40ter (accessed [today's date]).

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