Is AR p.Arg841Ser (c.2521C>A) pathogenic?

AR p.Arg841Ser (c.2521C>A) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9835); Absent from gnomAD v4.1; Associated with partial androgen insensitivity syndrome.

What condition is associated with AR p.Arg841Ser (c.2521C>A)?

AR p.Arg841Ser (c.2521C>A) is associated with partial androgen insensitivity syndrome (ClinVar).

How common is AR p.Arg841Ser (c.2521C>A) in the general population?

AR p.Arg841Ser (c.2521C>A) 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.Arg841Ser (c.2521C>A)?

AlphaMissense predicts likely pathogenic (score 0.9835) — an in-silico prediction, not a clinical call.

AR p.Arg841Ser

c.2521C>A · rs137852577 · VCV3250420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9835 · 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	0.9835	likely pathogenic
REVEL	0.883	moderately pathogenic-leaning
SaProt	LLR -9.70	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	24.3	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.Arg841Ser
Coding: c.2521C>A
MANE Select: NM_000044
dbSNP: rs137852577
Type: single nucleotide variant
Location: chrX:67722898 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 841: the nr lbd domain; the 'interaction with ccar1' region; the 'interaction with kat7' region; a UniProt-annotated variant site (in ais); a UniProt-annotated variant site (in pais); 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.Arg841Cys Pathogenic ★★ same residue
AR p.Arg841His 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-arg841ser (accessed [today's date]).

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