Is AMH p.Glu389Ter (c.1165G>T) pathogenic?

AMH p.Glu389Ter (c.1165G>T) is classified Pathogenic/Likely pathogenic in AMH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-05-06). Ultra-rare (popmax 0.0246%, eas); Associated with persistent Mullerian duct syndrome.

What condition is associated with AMH p.Glu389Ter (c.1165G>T)?

AMH p.Glu389Ter (c.1165G>T) is associated with persistent Mullerian duct syndrome (ClinVar).

How common is AMH p.Glu389Ter (c.1165G>T) in the general population?

AMH p.Glu389Ter (c.1165G>T) is ultra-rare (popmax 0.0246%, eas) (gnomAD).

AMH p.Glu389Ter

c.1165G>T · rs1415701260 · VCV1804920

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

ultra-rare (popmax 0.0246%, eas)

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	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP -0.18, phastCons 1
Overall
CADD	36.0	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 0.0246% East Asian · 8/32,562 alleles

Filtering AF 0.0122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.000556% 8/1,438,406 alleles · ultra-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.Glu389Ter
Coding: c.1165G>T
MANE Select: NM_000479
dbSNP: rs1415701260
Type: single nucleotide variant
Location: chr19:2251439 (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 389: an α-helix

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.Glu389Ala Uncertain significance ★ ⚠ same residue
AMH p.Arg40Ter Pathogenic/Likely pathogenic ★★ same condition
AMH p.Gln217Ter 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

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-glu389ter (accessed [today's date]).

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