Is AMH p.Pro144Ser (c.430C>T) pathogenic?

AMH p.Pro144Ser (c.430C>T) is classified Uncertain significance in AMH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: ambiguous (0.3731); Very rare (popmax 0.000138%).

How common is AMH p.Pro144Ser (c.430C>T) in the general population?

AMH p.Pro144Ser (c.430C>T) is very rare (popmax 0.000138%) (gnomAD).

What do computational predictors say about AMH p.Pro144Ser (c.430C>T)?

AlphaMissense predicts ambiguous (score 0.3731) — an in-silico prediction, not a clinical call.

AMH p.Pro144Ser

c.430C>T · VCV4692495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3731 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000138%)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3731	ambiguous
REVEL	0.277	benign-leaning
SaProt	LLR -9.41	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.73	GERP -0.32
Regional constraint	o/e 1.27	unconstrained · MANE · 2,621 bp · p 9.3e-15 · regional, not allelic
Overall
CADD	15.54	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 0.000138%

Overall 0.000138% 2/1,446,040 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.Pro144Ser
Coding: c.430C>T
MANE Select: NM_000479
Type: single nucleotide variant
Location: chr19:2250354 (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 144: a disulfide bond

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

Similar variants

AMH p.Pro144Ala 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-pro144ser (accessed [today's date]).

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