Is AMH p.Val12Gly (c.35T>G) pathogenic?

AMH p.Val12Gly (c.35T>G) is classified Uncertain significance in AMH (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-22). AlphaMissense: likely benign (0.0965); Rare (popmax 0.353%, nfe); Associated with Differences in sex development.

What condition is associated with AMH p.Val12Gly (c.35T>G)?

AMH p.Val12Gly (c.35T>G) is associated with Differences in sex development (ClinVar).

How common is AMH p.Val12Gly (c.35T>G) in the general population?

AMH p.Val12Gly (c.35T>G) is rare (popmax 0.353%, nfe) (gnomAD).

What do computational predictors say about AMH p.Val12Gly (c.35T>G)?

AlphaMissense predicts likely benign (score 0.0965) — an in-silico prediction, not a clinical call.

AMH p.Val12Gly

c.35T>G · rs149082963 · VCV381731

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0965 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.353%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Differences in sex development

Computational evidence

Protein change
AlphaMissense	0.0965	likely benign
REVEL	0.597	indeterminate
SaProt	LLR -6.72	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.79, phastCons 0.97
Regional constraint	o/e 1.27	unconstrained · MANE · 2,621 bp · p 9.3e-15 · regional, not allelic
Overall
CADD	12.26	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 0.353% European (non-Finnish) · 4,114/1,165,674 alleles

Filtering AF 0.344% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.34%

Overall 0.279% 4,411/1,582,944 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.353%	283
Amishnot grpmax-eligible	0.329%	304
Remaining individualsnot grpmax-eligible	0.239%	418
Admixed American	0.125%	803
Middle Eastern	0.0995%	1,005
Ashkenazi Jewishnot grpmax-eligible	0.0862%	1,160
African / African-American	0.0444%	2,251
Finnishnot grpmax-eligible	0.00841%	11,884
South Asian	0.00805%	12,421
East Asian	0.00232%	43,072

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.Val12Gly
Coding: c.35T>G
MANE Select: NM_000479
dbSNP: rs149082963
Type: single nucleotide variant
Location: chr19:2249367 (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 12: a UniProt-annotated variant site (in pmds1)

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

Disease context

Differences in sex development

Similar variants

AMH p.Gln217Ter Pathogenic/Likely pathogenic ★★ same condition
AMH p.Pro304Thr Uncertain significance ★★ ⚠ same condition
AMH p.Arg302Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
AMH p.His506Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
AMH p.Pro352Leu Uncertain significance ★ ⚠ same condition
AMH c.665-7A>G Likely benign same condition
AMH c.-2C>T Likely benign same condition
AMH p.Ser283= 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-val12gly (accessed [today's date]).

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