Is AR p.Gly461= (c.1383C>T) pathogenic?

AR p.Gly461= (c.1383C>T) is classified Likely benign in AR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-08). Rare (popmax 0.607%, sas); Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Gly461= (c.1383C>T)?

AR p.Gly461= (c.1383C>T) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Gly461= (c.1383C>T) in the general population?

AR p.Gly461= (c.1383C>T) is rare (popmax 0.607%, sas) (gnomAD).

AR p.Gly461=

c.1383C>T · rs768280979 · VCV506678

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.607%, sas)

Conditions

androgen insensitivity syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 0.16, phastCons 1
Overall
CADD	4.536	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.607% South Asian · 92/15,160 alleles

Filtering AF 0.507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.469%

Overall 0.129% 965/746,935 alleles · rare exomes 863/651,026 · genomes 102/95,909 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.32%	43
South Asiangrpmax	0.607%	165
Middle Eastern	0.517%	193
Remaining individualsnot grpmax-eligible	0.311%	322
Admixed American	0.106%	946
European (non-Finnish)	0.0925%	1,081
Finnishnot grpmax-eligible	0.0325%	3,075
African / African-American	0.0226%	4,417
East Asian	0.0157%	6,383

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AR
Protein: p.Gly461=
Coding: c.1383C>T
MANE Select: NM_000044
dbSNP: rs768280979
Type: single nucleotide variant
Location: chrX:67546529 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 461: 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

Also linked: Kennedy disease

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-gly461 (accessed [today's date]).

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