Is AR p.Ser741Cys (c.2222C>G) pathogenic?

AR p.Ser741Cys (c.2222C>G) is classified Pathogenic in AR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2004-03-01). AlphaMissense: likely pathogenic (0.6338); Absent from gnomAD v4.1; Associated with partial androgen insensitivity syndrome.

What condition is associated with AR p.Ser741Cys (c.2222C>G)?

AR p.Ser741Cys (c.2222C>G) is associated with partial androgen insensitivity syndrome (ClinVar).

How common is AR p.Ser741Cys (c.2222C>G) in the general population?

AR p.Ser741Cys (c.2222C>G) is absent from gnomAD v4.1 (gnomAD).

How is Partial androgen insensitivity syndrome inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about AR p.Ser741Cys (c.2222C>G)?

AlphaMissense predicts likely pathogenic (score 0.6338) — an in-silico prediction, not a clinical call.

AR p.Ser741Cys

c.2222C>G · rs137852601 · VCV9860

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6338 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

partial androgen insensitivity syndrome

Computational evidence

Protein change
AlphaMissense	0.6338	likely pathogenic ✓ concordant with ClinVar
REVEL	0.948	strongly pathogenic-leaning
SaProt	LLR -5.20	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ser741Cys
Coding: c.2222C>G
MANE Select: NM_000044
dbSNP: rs137852601
Type: single nucleotide variant
Location: chrX:67717526 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 741: the nr lbd domain; the 'interaction with ccar1' region; the 'interaction with kat7' region; an α-helix; the 'interaction with lpxn' region

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

Disease context

partial androgen insensitivity syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Partial androgen insensitivity syndrome (Orphanet):

Inheritance: X-linked recessive
Onset: All ages

Similar variants

AR p.Ser741Phe Pathogenic/Likely pathogenic ★★ ⚠ same residue
AR p.Ser741Pro Likely pathogenic ★ same residue
AR c.1768+2T>C Pathogenic/Likely pathogenic ★★ same condition
AR c.1769-11T>A Pathogenic ★★ same condition
AR p.Ala597Thr Pathogenic ★★ same condition
AR p.Ala871Val Pathogenic/Likely pathogenic ★★ same condition
AR p.Arg608Gln Pathogenic/Likely pathogenic ★★ same condition
AR p.Arg616His 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-ser741cys (accessed [today's date]).

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