Is AMH p.Thr268Ala (c.802A>G) pathogenic?

AMH p.Thr268Ala (c.802A>G) is classified Uncertain significance in AMH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-07-23). AlphaMissense: likely benign (0.0747); Ultra-rare (popmax 0.0442%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AMH p.Thr268Ala (c.802A>G)?

AMH p.Thr268Ala (c.802A>G) is associated with Inborn genetic diseases, persistent Mullerian duct syndrome (ClinVar).

How common is AMH p.Thr268Ala (c.802A>G) in the general population?

AMH p.Thr268Ala (c.802A>G) is ultra-rare (popmax 0.0442%, nfe) (gnomAD).

What do computational predictors say about AMH p.Thr268Ala (c.802A>G)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

AMH p.Thr268Ala

c.802A>G · rs201324658 · VCV1403680

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0442%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -5.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.99	GERP -2
Regional constraint	o/e 1.27	unconstrained · MANE · 2,621 bp · p 9.3e-15 · regional, not allelic
Overall
CADD	10.87	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0442% European (non-Finnish) · 503/1,139,184 alleles

Filtering AF 0.0409% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0396%

Overall 0.0366% 555/1,516,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0442%	2,265
Remaining individualsnot grpmax-eligible	0.0373%	2,682
Admixed American	0.0263%	3,807
Finnishnot grpmax-eligible	0.025%	4,005
Middle Eastern	0.0196%	5,114
African / African-American	0.00714%	14,011

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.Thr268Ala
Coding: c.802A>G
MANE Select: NM_000479
dbSNP: rs201324658
Type: single nucleotide variant
Location: chr19:2250986 (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 268: the 'disordered' region

Full AMH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: persistent Mullerian duct syndrome

Similar variants

AMH p.Thr268Ile Uncertain significance ★ ⚠ same residue
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.Arg219His Uncertain significance ★★ ⚠ same condition
AMH p.Asp192Gly 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-thr268ala (accessed [today's date]).

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