Is AMHR2 p.Arg71Gln (c.212G>A) pathogenic?

AMHR2 p.Arg71Gln (c.212G>A) is classified Likely benign in AMHR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely benign (0.0582); Ultra-rare (popmax 0.0167%, mid); Associated with Inborn genetic diseases.

What condition is associated with AMHR2 p.Arg71Gln (c.212G>A)?

AMHR2 p.Arg71Gln (c.212G>A) is associated with Inborn genetic diseases (ClinVar).

How common is AMHR2 p.Arg71Gln (c.212G>A) in the general population?

AMHR2 p.Arg71Gln (c.212G>A) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about AMHR2 p.Arg71Gln (c.212G>A)?

AlphaMissense predicts likely benign (score 0.0582) — an in-silico prediction, not a clinical call.

AMHR2 p.Arg71Gln

c.212G>A · rs767061692 · VCV2227039

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0582 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0582	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -6.33	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 -0.63	GERP -3.8
Regional constraint	o/e 0.89	unconstrained · MANE · 7,535 bp · p 0.0042 · regional, not allelic
Overall
CADD	4.978	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 0.0167% Middle Eastern · 1/5,990 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00062% 10/1,613,098 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,990
African / African-American	0.00267%	37,435
Admixed American	0.00167%	59,744
South Asian	0.0011%	90,960
European (non-Finnish)	0.000424%	235,939

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.Arg71Gln
Coding: c.212G>A
MANE Select: NM_020547
dbSNP: rs767061692
Type: single nucleotide variant
Location: chr12:53424450 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 1 PDB
Residue 71: a disulfide bond

Full AMHR2 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

AMHR2 p.Arg71= Likely benign ★ same residue
AMHR2 p.Ala139Val Uncertain significance ★★ ⚠ same condition
AMHR2 p.Arg22Gln Uncertain significance ★★ ⚠ same condition
AMHR2 p.Arg545Thr Uncertain significance ★★ ⚠ same condition
AMHR2 p.Cys551Tyr Uncertain significance ★★ ⚠ same condition
AMHR2 p.Ser432Asn Uncertain significance ★★ ⚠ same condition
AMHR2 p.Trp367Cys Uncertain significance ★★ ⚠ same condition
AMHR2 p.Arg59His 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/amhr2-p-arg71gln (accessed [today's date]).

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