Is AMH p.Pro203Ser (c.607C>T) pathogenic?

AMH p.Pro203Ser (c.607C>T) is classified Uncertain significance in AMH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-28). AlphaMissense: ambiguous (0.3636); Ultra-rare (popmax 0.0301%, afr); Associated with Inborn genetic diseases.

What condition is associated with AMH p.Pro203Ser (c.607C>T)?

AMH p.Pro203Ser (c.607C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AMH p.Pro203Ser (c.607C>T) in the general population?

AMH p.Pro203Ser (c.607C>T) is ultra-rare (popmax 0.0301%, afr) (gnomAD).

What do computational predictors say about AMH p.Pro203Ser (c.607C>T)?

AlphaMissense predicts ambiguous (score 0.3636) — an in-silico prediction, not a clinical call.

AMH p.Pro203Ser

c.607C>T · rs755678822 · VCV2394380

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3636 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0301%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3636	ambiguous
REVEL	0.238	benign-leaning
SaProt	LLR -10.34	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1, phastCons 0.68
Regional constraint	o/e 1.27	unconstrained · MANE · 2,621 bp · p 9.3e-15 · regional, not allelic
Overall
CADD	18.45	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 0.0301% African / African-American · 22/73,140 alleles

Filtering AF 0.0203% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00162% 25/1,538,804 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0301%	3,325
South Asian	0.00238%	42,061
Remaining individualsnot grpmax-eligible	0.00167%	59,914

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.Pro203Ser
Coding: c.607C>T
MANE Select: NM_000479
dbSNP: rs755678822
Type: single nucleotide variant
Location: chr19:2250703 (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-pro203ser (accessed [today's date]).

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