Is AR p.Cys596= (c.1788C>T) pathogenic?

AR p.Cys596= (c.1788C>T) is classified Benign in AR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). Low-frequency (popmax 1.09%, afr); Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Cys596= (c.1788C>T)?

AR p.Cys596= (c.1788C>T) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Cys596= (c.1788C>T) in the general population?

AR p.Cys596= (c.1788C>T) is low-frequency (popmax 1.09%, afr) (gnomAD).

AR p.Cys596=

c.1788C>T · rs150303722 · VCV1170227

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.09%, 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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -2, phastCons 1
Overall
CADD	8.636	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.09% African / African-American · 621/57,197 alleles

Filtering AF 1.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.987%

Overall 0.111% 1,341/1,207,718 alleles · low-frequency exomes 971/1,095,614 · genomes 370/112,104 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.09%	92
Ashkenazi Jewishnot grpmax-eligible	0.836%	120
South Asian	0.712%	141
Remaining individualsnot grpmax-eligible	0.137%	731
Admixed American	0.0437%	2,289
Middle Eastern	0.023%	4,345
Finnishnot grpmax-eligible	0.0172%	5,824
European (non-Finnish)	0.00425%	23,503

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.Cys596=
Coding: c.1788C>T
MANE Select: NM_000044
dbSNP: rs150303722
Type: single nucleotide variant
Location: chrX:67686029 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 596: the 'interaction with hipk3' region; the 'interaction with ccar1' region; a DNA-binding 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

Also linked: Kennedy disease

Similar variants

AR p.Cys596Arg Likely pathogenic ★ same residue
AR p.Cys596Tyr Likely pathogenic ★ same residue
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

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-cys596 (accessed [today's date]).

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