Is AMHR2 p.Arg22Ter (c.64C>T) pathogenic?

AMHR2 p.Arg22Ter (c.64C>T) is classified Pathogenic/Likely pathogenic in AMHR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-09). Very rare (popmax 0.00446%, eas); Associated with persistent Mullerian duct syndrome.

What condition is associated with AMHR2 p.Arg22Ter (c.64C>T)?

AMHR2 p.Arg22Ter (c.64C>T) is associated with persistent Mullerian duct syndrome (ClinVar).

How common is AMHR2 p.Arg22Ter (c.64C>T) in the general population?

AMHR2 p.Arg22Ter (c.64C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

AMHR2 p.Arg22Ter

c.64C>T · rs755196112 · VCV1338211

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 0.00446%, 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	predicted	premature termination codon in exon 2 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1.2, phastCons 1
Overall
CADD	37.0	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 0.00446% East Asian · 2/44,886 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.00105% 17/1,612,548 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,443
Admixed American	0.00167%	60,014
Remaining individualsnot grpmax-eligible	0.0016%	62,364
Finnishnot grpmax-eligible	0.00156%	64,030
African / African-American	0.00133%	74,982
South Asian	0.0011%	91,002
European (non-Finnish)	0.000847%	118,003

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.Arg22Ter
Coding: c.64C>T
MANE Select: NM_020547
dbSNP: rs755196112
Type: single nucleotide variant
Location: chr12:53424302 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 1 PDB

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.Arg22Gln Uncertain significance ★★ ⚠ same residue
AMHR2 p.Arg172Ter 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-arg22ter (accessed [today's date]).

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