Is AMH p.Arg202Cys (c.604C>T) pathogenic?

AMH p.Arg202Cys (c.604C>T) is classified Uncertain significance in AMH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). AlphaMissense: likely benign (0.2171); Ultra-rare (popmax 0.0341%, eas).

How common is AMH p.Arg202Cys (c.604C>T) in the general population?

AMH p.Arg202Cys (c.604C>T) is ultra-rare (popmax 0.0341%, eas) (gnomAD).

What do computational predictors say about AMH p.Arg202Cys (c.604C>T)?

AlphaMissense predicts likely benign (score 0.2171) — an in-silico prediction, not a clinical call.

AMH p.Arg202Cys

c.604C>T · rs752186483 · VCV1355108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2171 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0341%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2171	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -11.58	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP 1
Regional constraint	o/e 1.27	unconstrained · MANE · 2,621 bp · p 9.3e-15 · regional, not allelic
Overall
CADD	18.78	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 0.0341% East Asian · 14/41,090 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0165%

Overall 0.00123% 19/1,539,262 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0341%	2,935
Remaining individualsnot grpmax-eligible	0.00334%	29,956
European (non-Finnish)	0.000261%	382,570

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.Arg202Cys
Coding: c.604C>T
MANE Select: NM_000479
dbSNP: rs752186483
Type: single nucleotide variant
Location: chr19:2250700 (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.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
AMH p.Ala78Thr Uncertain significance ★★ ⚠ 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-arg202cys (accessed [today's date]).

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