Is AMH p.Leu320Pro (c.959T>C) pathogenic?

AMH p.Leu320Pro (c.959T>C) is classified Uncertain significance in AMH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: ambiguous (0.4147); Very rare (popmax 7.4e-05%); Associated with Inborn genetic diseases.

What condition is associated with AMH p.Leu320Pro (c.959T>C)?

AMH p.Leu320Pro (c.959T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AMH p.Leu320Pro (c.959T>C) in the general population?

AMH p.Leu320Pro (c.959T>C) is very rare (popmax 7.4e-05%) (gnomAD).

What do computational predictors say about AMH p.Leu320Pro (c.959T>C)?

AlphaMissense predicts ambiguous (score 0.4147) — an in-silico prediction, not a clinical call.

AMH p.Leu320Pro

c.959T>C · VCV4046732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4147 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.4e-05%)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4147	ambiguous
REVEL	0.516	indeterminate
SaProt	LLR -6.30	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 2,621 bp · p 9.3e-15 · regional, not allelic
Overall
CADD	22.4	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 7.4e-05%

Overall 7.4e-05% 1/1,350,442 alleles · very rare

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.Leu320Pro
Coding: c.959T>C
MANE Select: NM_000479
Type: single nucleotide variant
Location: chr19:2251233 (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

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

Similar variants

AMH p.Arg219His Uncertain significance ★★ ⚠ same condition
AMH p.Asp192Gly Uncertain significance ★★ ⚠ same condition
AMH p.Glu256Gln Uncertain significance ★★ ⚠ same condition
AMH p.Pro168Thr Uncertain significance ★★ ⚠ same condition
AMH p.Pro46His Uncertain significance ★★ ⚠ same condition
AMH p.Thr268Ala Uncertain significance ★★ ⚠ same condition
AMH p.Ala162Val Uncertain significance ★ ⚠ same condition
AMH p.Ala18Thr 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-leu320pro (accessed [today's date]).

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