Is AR p.Gln488Ter (c.1462C>T) pathogenic?

AR p.Gln488Ter (c.1462C>T) is classified Pathogenic in AR (ClinVar, Single submitter, 2 submitters; last evaluated 2017-10-12). Absent from gnomAD v4.1; Associated with 46,XY complete gonadal dysgenesis.

What condition is associated with AR p.Gln488Ter (c.1462C>T)?

AR p.Gln488Ter (c.1462C>T) is associated with 46,XY complete gonadal dysgenesis (ClinVar).

How common is AR p.Gln488Ter (c.1462C>T) in the general population?

AR p.Gln488Ter (c.1462C>T) is absent from gnomAD v4.1 (gnomAD).

AR p.Gln488Ter

c.1462C>T · rs1929774367 · VCV988321

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

46,XY complete gonadal dysgenesis

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 1 of 8
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.2, phastCons 1
Overall
CADD	36.0	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.Gln488Ter
Coding: c.1462C>T
MANE Select: NM_000044
dbSNP: rs1929774367
Type: single nucleotide variant
Location: chrX:67546608 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 488: the 'interaction with znf318' region; the 'modulating' region

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

Disease context

46,XY complete gonadal dysgenesis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AR p.Gln488fs Pathogenic ★ same residue
AR c.1768+2T>C Pathogenic/Likely pathogenic ★★ same type
AR c.1769-11T>A Pathogenic ★★ same type
AR c.2450-6C>G Pathogenic ★★ same type
AR p.Ala588Pro Pathogenic/Likely pathogenic ★★ same type
AR p.Ala597Thr Pathogenic ★★ same type
AR p.Ala688Val Pathogenic/Likely pathogenic ★★ same type
AR p.Ala766Thr Pathogenic ★★ same type

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-gln488ter (accessed [today's date]).

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