Is AMHR2 p.Arg562Ser (c.1686G>C) pathogenic?

AMHR2 p.Arg562Ser (c.1686G>C) is classified Uncertain significance in AMHR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-24). AlphaMissense: likely benign (0.1486); Ultra-rare (popmax 0.0493%, mid).

How common is AMHR2 p.Arg562Ser (c.1686G>C) in the general population?

AMHR2 p.Arg562Ser (c.1686G>C) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about AMHR2 p.Arg562Ser (c.1686G>C)?

AlphaMissense predicts likely benign (score 0.1486) — an in-silico prediction, not a clinical call.

AMHR2 p.Arg562Ser

c.1686G>C · rs778363612 · VCV1348508

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1486 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1486	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -5.10	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 2.2	GERP -3.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 7,535 bp · p 0.0042 · regional, not allelic
Overall
CADD	15.14	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00136% 22/1,614,098 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
European (non-Finnish)	0.00153%	65,558
African / African-American	0.00133%	74,942

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: AMHR2
Protein: p.Arg562Ser
Coding: c.1686G>C
MANE Select: NM_020547
dbSNP: rs778363612
Type: single nucleotide variant
Location: chr12:53431437 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 1 PDB

Full AMHR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMHR2 p.Ala168Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
AMHR2 p.Arg172Ter Pathogenic/Likely pathogenic ★★ same type
AMHR2 p.Arg22Ter Pathogenic/Likely pathogenic ★★ same type
AMHR2 p.Arg463Cys Pathogenic/Likely pathogenic ★★ same type
AMHR2 p.Arg471His Pathogenic/Likely pathogenic ★★ ⚠ same type
AMHR2 p.Ala118Thr Uncertain significance ★★ ⚠ same type
AMHR2 p.Ala139Val Uncertain significance ★★ ⚠ same type
AMHR2 p.Arg22Gln 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/amhr2-p-arg562ser (accessed [today's date]).

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