Is AR p.Glu645Ter (c.1933G>T) pathogenic?

AR p.Glu645Ter (c.1933G>T) is classified Likely pathogenic in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Absent from gnomAD v4.1; Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Glu645Ter (c.1933G>T)?

AR p.Glu645Ter (c.1933G>T) is associated with androgen insensitivity syndrome (ClinVar).

How common is AR p.Glu645Ter (c.1933G>T) in the general population?

AR p.Glu645Ter (c.1933G>T) is absent from gnomAD v4.1 (gnomAD).

AR p.Glu645Ter

c.1933G>T · rs2147524252 · VCV1705712

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

androgen insensitivity syndrome

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	predicted	premature termination codon in exon 4 of 8
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.7, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AR
Protein: p.Glu645Ter
Coding: c.1933G>T
MANE Select: NM_000044
dbSNP: rs2147524252
Type: single nucleotide variant
Location: chrX:67711449 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 645: the 'interaction with hipk3' region; the 'interaction with ccar1' region; the 'interaction with kat7' region; 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

Similar variants

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
AR p.Ala766Thr Pathogenic ★★ same condition
AR p.Ala871Val 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-glu645ter (accessed [today's date]).

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