Is AMH p.Ala206Pro (c.616G>C) pathogenic?

AMH p.Ala206Pro (c.616G>C) is classified Uncertain significance in AMH (ClinVar, Single submitter, 1 submitter; last evaluated 2016-10-28). AlphaMissense: ambiguous (0.3905); Ultra-rare (popmax 0.0218%, afr).

How common is AMH p.Ala206Pro (c.616G>C) in the general population?

AMH p.Ala206Pro (c.616G>C) is ultra-rare (popmax 0.0218%, afr) (gnomAD).

What do computational predictors say about AMH p.Ala206Pro (c.616G>C)?

AlphaMissense predicts ambiguous (score 0.3905) — an in-silico prediction, not a clinical call.

AMH p.Ala206Pro

c.616G>C · rs558720829 · VCV390467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3905 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0218%, afr)

Computational evidence

Protein change
AlphaMissense	0.3905	ambiguous
REVEL	0.479	indeterminate
SaProt	LLR -10.25	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 1, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 2,621 bp · p 9.3e-15 · regional, not allelic
Overall
CADD	23.4	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 0.0218% African / African-American · 16/73,258 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.0011% 17/1,538,616 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0218%	4,579
European (non-Finnish)	8.71e-05%	1,147,742

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.Ala206Pro
Coding: c.616G>C
MANE Select: NM_000479
dbSNP: rs558720829
Type: single nucleotide variant
Location: chr19:2250712 (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

Similar variants

AMH p.Ala206Val Uncertain significance ★ ⚠ same residue
AMH p.Arg40Ter Pathogenic/Likely pathogenic ★★ same type
AMH p.Gln217Ter Pathogenic/Likely pathogenic ★★ same type
AMH p.Glu389Ter Pathogenic/Likely pathogenic ★★ same type
AMH p.Gly101Arg Likely pathogenic ★★ same type
AMH p.Pro151Ser Pathogenic ★★ ⚠ same type
AMH p.Trp371Ter Pathogenic ★★ same type
AMH p.Tyr167Cys Pathogenic ★★ same type

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-ala206pro (accessed [today's date]).

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