Is AR p.Arg539fs (c.1614dup) pathogenic?

AR p.Arg539fs (c.1614dup) is classified Pathogenic in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-21). No gnomAD frequency available for this variant; Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Arg539fs (c.1614dup)?

AR p.Arg539fs (c.1614dup) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Arg539fs (c.1614dup) in the general population?

AR p.Arg539fs (c.1614dup) is no gnomAD frequency available for this variant (gnomAD).

AR p.Arg539fs

c.1614dup · rs1569265470 · VCV578903

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

androgen insensitivity syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Arg539fs
Coding: c.1614dup
MANE Select: NM_000044
dbSNP: rs1569265470
Type: Duplication
Location: chrX:67546759 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 539: the 'interaction with znf318' region; the 'modulating' region

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

Disease context

androgen insensitivity syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Kennedy disease

Similar variants

AR p.Gln803fs Pathogenic ★★ same condition
AR c.2449+1_2449+3dup Likely pathogenic ★ same condition
AR p.Ala401fs Likely pathogenic ★ same condition
AR p.Ala722fs Pathogenic ★ same condition
AR p.Asp183fs Pathogenic ★ same condition
AR p.Gly337fs Pathogenic ★ same condition
AR p.Gly448fs Pathogenic ★ same condition
AR p.His384fs 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-arg539fs (accessed [today's date]).

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