Is AR p.Gly451= (c.1353T>C) pathogenic?

AR p.Gly451= (c.1353T>C) is classified Likely benign in AR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-16). Very rare (popmax 0.000687%, nfe); Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Gly451= (c.1353T>C)?

AR p.Gly451= (c.1353T>C) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Gly451= (c.1353T>C) in the general population?

AR p.Gly451= (c.1353T>C) is very rare (popmax 0.000687%, nfe) (gnomAD).

AR p.Gly451=

c.1353T>C · rs1406846471 · VCV2935824

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000687%, nfe)

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 -0.54	GERP -1.3, phastCons 0.86
Overall
CADD	10.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000687% European (non-Finnish) · 5/727,881 alleles

Filtering AF 0.000201% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000146%

Overall 0.00539% 5/92,786 alleles · very rare

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.Gly451=
Coding: c.1353T>C
MANE Select: NM_000044
dbSNP: rs1406846471
Type: single nucleotide variant
Location: chrX:67546499 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 451: 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-gly451 (accessed [today's date]).

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