Is AR p.Pro449fs (c.1344_1345insTA) pathogenic?

AR p.Pro449fs (c.13441345insTA) is classified Pathogenic in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-04). Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Pro449fs (c.1344_1345insTA)?

AR p.Pro449fs (c.1344_1345insTA) is associated with androgen insensitivity syndrome (ClinVar).

AR p.Pro449fs

c.1344_1345insTA · VCV3336688

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 1 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 1.1, phastCons 1

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

Variant & gene context

Gene: AR
Protein: p.Pro449fs
Coding: c.1344_1345insTA
MANE Select: NM_000044
Type: Insertion
Location: chrX:67546489 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 449: 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

Similar variants

AR p.Pro449= Likely benign ★ same residue
AR p.Gly470_Gly473dup Benign/Likely benign ★★ same condition
AR p.Gln115delinsHisArgTer Pathogenic ★ same condition
AR p.Gln62Ter Pathogenic ★ same condition
AR p.Glu81fs Pathogenic ★ same condition
AR p.Leu57_Gln58insLeuGlnGln Conflicting classifications of pathogenicity ★ same condition
AR p.Leu57_Gln58insLeuGlnGlnGlnGln Uncertain significance ★ same condition
AR p.Leu57_Gln58insLeuGlnGlnGlnGlnGlnGln 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-pro449fs (accessed [today's date]).

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