Is AR p.Leu57del (c.161TGC[3]) pathogenic?

AR p.Leu57del (c.161TGC[3]) is classified Likely benign in AR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-31). Ultra-rare (popmax 0.0813%, afr); Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Leu57del (c.161TGC[3])?

AR p.Leu57del (c.161TGC[3]) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Leu57del (c.161TGC[3]) in the general population?

AR p.Leu57del (c.161TGC[3]) is ultra-rare (popmax 0.0813%, afr) (gnomAD).

AR p.Leu57del

c.161TGC[3] · rs752055010 · VCV807734

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0813%, afr)

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 · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP 2.1, phastCons 1
Overall
CADD	16.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0813% African / African-American · 40/49,190 alleles

Filtering AF 0.0613% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0543%

Overall 0.0102% 117/1,143,649 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0813%	1,230
South Asian	0.0702%	1,424
Remaining individualsnot grpmax-eligible	0.0134%	7,488
East Asian	0.0101%	9,891
European (non-Finnish)	0.00348%	28,768
Admixed American	0.00252%	39,610

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.Leu57del
Coding: c.161TGC[3]
MANE Select: NM_000044
dbSNP: rs752055010
Type: Microsatellite
Location: chrX:67545307 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 57: a UniProt-annotated variant site (in prostate cancer); the 'interaction with znf318' region; the 'modulating' region; the 'disordered' 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 p.Leu57dup Conflicting classifications of pathogenicity ★ same residue
AR p.Leu57Gln Benign/Likely benign ★★ same residue
AR p.Leu57_Gln58insLeu Likely pathogenic ★ same residue
AR p.Leu57_Gln58insLeuGlnGln Conflicting classifications of pathogenicity ★ same residue
AR p.Leu57_Gln58insLeuGlnGlnGlnGln Uncertain significance ★ same residue
AR p.Leu57_Gln58insLeuGlnGlnGlnGlnGlnGln Uncertain significance ★ same residue
AR p.Gly462_Gly473del Uncertain significance ★★ same condition
AR p.Gln69_Gln80del Benign/Likely benign ★★ 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-leu57del (accessed [today's date]).

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