Is AMH p.Pro352Leu (c.1055C>T) pathogenic?

AMH p.Pro352Leu (c.1055C>T) is classified Uncertain significance in AMH (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-22). AlphaMissense: likely benign (0.1996); Ultra-rare (popmax 0.0231%, mid); Associated with Differences in sex development.

What condition is associated with AMH p.Pro352Leu (c.1055C>T)?

AMH p.Pro352Leu (c.1055C>T) is associated with Differences in sex development (ClinVar).

How common is AMH p.Pro352Leu (c.1055C>T) in the general population?

AMH p.Pro352Leu (c.1055C>T) is ultra-rare (popmax 0.0231%, mid) (gnomAD).

What do computational predictors say about AMH p.Pro352Leu (c.1055C>T)?

AlphaMissense predicts likely benign (score 0.1996) — an in-silico prediction, not a clinical call.

AMH p.Pro352Leu

c.1055C>T · VCV4820642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1996 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Differences in sex development

Computational evidence

Protein change
AlphaMissense	0.1996	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -8.32	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 1.1	GERP 0.17, phastCons 0.049
Regional constraint	o/e 1.27	unconstrained · MANE · 2,621 bp · p 9.3e-15 · regional, not allelic
Overall
CADD	16.97	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 0.0231% Middle Eastern · 1/4,324 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00112%

Overall 0.001% 15/1,496,182 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0231%	4,324
African / African-American	0.00583%	17,156
South Asian	0.00375%	26,677
Remaining individualsnot grpmax-eligible	0.00172%	57,994
European (non-Finnish)	0.000531%	188,409

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.Pro352Leu
Coding: c.1055C>T
MANE Select: NM_000479
Type: single nucleotide variant
Location: chr19:2251329 (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

Differences in sex development

Similar variants

AMH p.Pro352Ser Uncertain significance ★★ ⚠ same residue
AMH p.Pro352= Likely benign ★ same residue
AMH p.Gln217Ter Pathogenic/Likely pathogenic ★★ same condition
AMH p.Pro304Thr Uncertain significance ★★ ⚠ same condition
AMH p.Val12Gly Uncertain significance ★★ ⚠ same condition
AMH p.Arg302Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
AMH p.His506Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
AMH c.665-7A>G 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-pro352leu (accessed [today's date]).

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