Is AMH p.Ala86= (c.258C>T) pathogenic?

AMH p.Ala86= (c.258C>T) is classified Benign/Likely benign in AMH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-15). Rare (popmax 0.356%, afr); Associated with persistent Mullerian duct syndrome.

What condition is associated with AMH p.Ala86= (c.258C>T)?

AMH p.Ala86= (c.258C>T) is associated with persistent Mullerian duct syndrome (ClinVar).

How common is AMH p.Ala86= (c.258C>T) in the general population?

AMH p.Ala86= (c.258C>T) is rare (popmax 0.356%, afr) (gnomAD).

AMH p.Ala86=

c.258C>T · VCV3377282

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.356%, afr)

Conditions

persistent Mullerian duct syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -1.6
Overall
CADD	0.158	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.356% African / African-American · 263/73,784 alleles

Filtering AF 0.321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.307%

Overall 0.0231% 361/1,560,004 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.356%	281
Remaining individualsnot grpmax-eligible	0.0447%	2,236
Admixed American	0.0376%	2,657
South Asian	0.0174%	5,761
Middle Eastern	0.0169%	5,918
European (non-Finnish)	0.00294%	33,963
Finnishnot grpmax-eligible	0.00186%	53,850

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.Ala86=
Coding: c.258C>T
MANE Select: NM_000479
Type: single nucleotide variant
Location: chr19:2249590 (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.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-ala86 (accessed [today's date]).

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