Is AMH p.Pro151Ser (c.451C>T) pathogenic?

AMH p.Pro151Ser (c.451C>T) is classified Pathogenic in AMH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-16). AlphaMissense: likely benign (0.3343); Ultra-rare (popmax 0.0127%, nfe); Associated with persistent Mullerian duct syndrome.

What condition is associated with AMH p.Pro151Ser (c.451C>T)?

AMH p.Pro151Ser (c.451C>T) is associated with persistent Mullerian duct syndrome (ClinVar).

How common is AMH p.Pro151Ser (c.451C>T) in the general population?

AMH p.Pro151Ser (c.451C>T) is ultra-rare (popmax 0.0127%, nfe) (gnomAD).

What do computational predictors say about AMH p.Pro151Ser (c.451C>T)?

AlphaMissense predicts likely benign (score 0.3343) — an in-silico prediction, not a clinical call.

AMH p.Pro151Ser

c.451C>T · VCV3665082

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3343 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0127%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

persistent Mullerian duct syndrome

Computational evidence

Protein change
AlphaMissense	0.3343	likely benign ⚠ discordant with ClinVar
REVEL	0.446	indeterminate
SaProt	LLR -11.37	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.79, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 2,621 bp · p 9.3e-15 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0127% European (non-Finnish) · 149/1,172,824 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0104%

Overall 0.00985% 157/1,594,648 alleles · ultra-rare exomes 144/1,442,490 · genomes 13/152,158 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0127%	7,871
Remaining individualsnot grpmax-eligible	0.0081%	12,346
Admixed American	0.00347%	28,812
Ashkenazi Jewishnot grpmax-eligible	0.00343%	29,162

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.Pro151Ser
Coding: c.451C>T
MANE Select: NM_000479
Type: single nucleotide variant
Location: chr19:2250375 (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.Arg40Ter Pathogenic/Likely pathogenic ★★ same condition
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.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-pro151ser (accessed [today's date]).

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