Is AMHR2 p.Arg97Ter (c.289C>T) pathogenic?

AMHR2 p.Arg97Ter (c.289C>T) is classified Pathogenic in AMHR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). Ultra-rare (popmax 0.0164%, mid); Associated with persistent Mullerian duct syndrome.

What condition is associated with AMHR2 p.Arg97Ter (c.289C>T)?

AMHR2 p.Arg97Ter (c.289C>T) is associated with persistent Mullerian duct syndrome (ClinVar).

How common is AMHR2 p.Arg97Ter (c.289C>T) in the general population?

AMHR2 p.Arg97Ter (c.289C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

AMHR2 p.Arg97Ter

c.289C>T · VCV3574978

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 3 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.006	GERP -3.9, phastCons 0.66
Overall
CADD	35.0	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00161% 26/1,613,774 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
African / African-American	0.00935%	10,695
East Asian	0.00446%	22,441
South Asian	0.0022%	45,534
European (non-Finnish)	0.00119%	84,280

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: AMHR2
Protein: p.Arg97Ter
Coding: c.289C>T
MANE Select: NM_020547
Type: single nucleotide variant
Location: chr12:53424765 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 1 PDB
Residue 97: a disulfide bond; a β-strand

Full AMHR2 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

AMHR2 p.Arg172Ter Pathogenic/Likely pathogenic ★★ same condition
AMHR2 p.Arg22Ter Pathogenic/Likely pathogenic ★★ same condition
AMHR2 p.Arg463Cys Pathogenic/Likely pathogenic ★★ same condition
AMHR2 p.Arg471His Pathogenic/Likely pathogenic ★★ ⚠ same condition
AMHR2 c.622-6C>T Benign/Likely benign ★★ same condition
AMHR2 c.622-1G>A Likely pathogenic ★ same condition
AMHR2 p.Arg259Ter Pathogenic ★ same condition
AMHR2 p.Arg332Ter Pathogenic ★ 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/amhr2-p-arg97ter (accessed [today's date]).

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