Is AR p.Lys778fs (c.2329_2333dup) pathogenic?

AR p.Lys778fs (c.23292333dup) is classified Pathogenic in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Lys778fs (c.2329_2333dup)?

AR p.Lys778fs (c.2329_2333dup) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

AR p.Lys778fs

c.2329_2333dup · VCV4786681

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 6 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1

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

Variant & gene context

Gene: AR
Protein: p.Lys778fs
Coding: c.2329_2333dup
MANE Select: NM_000044
Type: Duplication
Location: chrX:67721842 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 778: the nr lbd domain; the 'interaction with ccar1' region; the 'interaction with kat7' region; an α-helix; the 'interaction with lpxn' 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.Lys778Asn Uncertain significance ★★ ⚠ same residue
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.Arg539fs Pathogenic ★ same condition
AR p.Asp183fs Pathogenic ★ same condition
AR p.Gly337fs 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-lys778fs (accessed [today's date]).

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