Is AR p.Arg20Gln (c.59G>A) pathogenic?

AR p.Arg20Gln (c.59G>A) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: ambiguous (0.4583); Very rare (popmax 0.000112%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AR p.Arg20Gln (c.59G>A)?

AR p.Arg20Gln (c.59G>A) is associated with Inborn genetic diseases (ClinVar).

How common is AR p.Arg20Gln (c.59G>A) in the general population?

AR p.Arg20Gln (c.59G>A) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about AR p.Arg20Gln (c.59G>A)?

AlphaMissense predicts ambiguous (score 0.4583) — an in-silico prediction, not a clinical call.

AR p.Arg20Gln

c.59G>A · VCV4129409

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4583 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4583	ambiguous
REVEL	0.684	pathogenic-leaning
SaProt	LLR -6.27	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 2.1, phastCons 1
Overall
CADD	25.1	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 0.000112% European (non-Finnish) · 1/894,288 alleles

Overall 9.12e-05% 1/1,096,219 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: AR
Protein: p.Arg20Gln
Coding: c.59G>A
MANE Select: NM_000044
Type: single nucleotide variant
Location: chrX:67545205 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 20: the 'interaction with znf318' region; the 'modulating' region

Full AR 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

AR p.Leu446Trp Uncertain significance ★★ ⚠ same condition
AR p.Gly471= Likely benign ★★ same condition
AR p.Ala151Glu Uncertain significance ★ ⚠ same condition
AR p.Ala253Gly Uncertain significance ★ ⚠ same condition
AR p.Ala331Asp Uncertain significance ★ ⚠ same condition
AR p.Ala358Glu Uncertain significance ★ ⚠ same condition
AR p.Ala477Pro Uncertain significance ★ ⚠ same condition
AR p.Arg13Gly 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/ar-p-arg20gln (accessed [today's date]).

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