Is AR p.Glu474= (c.1422G>A) pathogenic?

AR p.Glu474= (c.1422G>A) is classified Likely benign in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). No allele count reported in gnomAD v4.1 (AN 1,005,140); Associated with Kennedy disease.

What condition is associated with AR p.Glu474= (c.1422G>A)?

AR p.Glu474= (c.1422G>A) is associated with Kennedy disease, androgen insensitivity syndrome (ClinVar).

How common is AR p.Glu474= (c.1422G>A) in the general population?

AR p.Glu474= (c.1422G>A) is no allele count reported in gnomAD v4.1 (AN 1,005,140) (gnomAD).

How is Kennedy disease inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AR p.Glu474=

c.1422G>A · rs1171987220 · VCV2938146

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,005,140)

Conditions

Kennedy disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.21	GERP -0.93, phastCons 0.003
Overall
CADD	3.554	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,005,140). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AR
Protein: p.Glu474=
Coding: c.1422G>A
MANE Select: NM_000044
dbSNP: rs1171987220
Type: single nucleotide variant
Location: chrX:67546568 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 474: the 'interaction with znf318' region; the 'modulating' region

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

Disease context

Kennedy disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: androgen insensitivity syndrome

For Kennedy disease (Orphanet):

Inheritance: X-linked recessive
Onset: Adult
Prevalence: <1 / 1 000 000 (Italy)

Similar variants

AR p.Glu474del Uncertain significance ★ same residue
AR p.Glu474Gly Likely pathogenic ★ ⚠ same residue
AR c.1768+2T>C Pathogenic/Likely pathogenic ★★ same condition
AR c.1769-11T>A Pathogenic ★★ same condition
AR c.2450-6C>G Pathogenic ★★ same condition
AR p.Ala588Pro Pathogenic/Likely pathogenic ★★ same condition
AR p.Ala597Thr Pathogenic ★★ same condition
AR p.Ala688Val Pathogenic/Likely pathogenic ★★ 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-glu474 (accessed [today's date]).

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