Is AMH p.Ala521Val (c.1562C>T) pathogenic?

AMH p.Ala521Val (c.1562C>T) is classified Likely benign in AMH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-17). AlphaMissense: likely benign (0.176); Rare (popmax 0.103%, eas).

How common is AMH p.Ala521Val (c.1562C>T) in the general population?

AMH p.Ala521Val (c.1562C>T) is rare (popmax 0.103%, eas) (gnomAD).

What do computational predictors say about AMH p.Ala521Val (c.1562C>T)?

AlphaMissense predicts likely benign (score 0.176) — an in-silico prediction, not a clinical call.

AMH p.Ala521Val

c.1562C>T · rs368432946 · VCV1593294

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.176 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.176	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -9.13	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 1.6	GERP -0.21, phastCons 0.89
Regional constraint	o/e 1.27	unconstrained · MANE · 2,621 bp · p 9.3e-15 · regional, not allelic
Overall
CADD	20.3	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 0.103% East Asian · 46/44,626 alleles

Filtering AF 0.0794% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.071%

Overall 0.005% 80/1,599,628 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.103%	970
South Asian	0.0254%	3,933
Remaining individualsnot grpmax-eligible	0.0113%	8,875
Admixed American	0.00168%	59,570
European (non-Finnish)	0.000255%	392,502

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.Ala521Val
Coding: c.1562C>T
MANE Select: NM_000479
dbSNP: rs368432946
Type: single nucleotide variant
Location: chr19:2251836 (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 521: a disulfide bond; a β-strand; the 'muellerian-inhibiting factor chain dimerization' region

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

Similar variants

AMH p.Ala521= Benign ★ 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-ala521val (accessed [today's date]).

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