Is AR p.Tyr774Ter (c.2319_2321dup) pathogenic?

AR p.Tyr774Ter (c.23192321dup) is classified Pathogenic in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-31). No gnomAD frequency available for this variant; Associated with Kennedy disease.

What condition is associated with AR p.Tyr774Ter (c.2319_2321dup)?

AR p.Tyr774Ter (c.2319_2321dup) is associated with Kennedy disease, androgen insensitivity syndrome (ClinVar).

How common is AR p.Tyr774Ter (c.2319_2321dup) in the general population?

AR p.Tyr774Ter (c.2319_2321dup) is no gnomAD frequency available for this variant (gnomAD).

How is Kennedy disease inherited?

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

AR p.Tyr774Ter

c.2319_2321dup · rs2147535489 · VCV1394063

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Kennedy disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
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.

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.Tyr774Ter
Coding: c.2319_2321dup
MANE Select: NM_000044
dbSNP: rs2147535489
Type: Duplication
Location: chrX:67721832 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 774: 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

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.Tyr774= Likely benign ★ 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-tyr774ter (accessed [today's date]).

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