Is AR p.Arg761Ser (c.2283G>T) pathogenic?

AR p.Arg761Ser (c.2283G>T) is classified Conflicting classifications of pathogenicity in AR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-04-01). AlphaMissense: likely pathogenic (0.9823); Very rare (popmax 0.000223%, nfe); Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Arg761Ser (c.2283G>T)?

AR p.Arg761Ser (c.2283G>T) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Arg761Ser (c.2283G>T) in the general population?

AR p.Arg761Ser (c.2283G>T) is very rare (popmax 0.000223%, nfe) (gnomAD).

What do computational predictors say about AR p.Arg761Ser (c.2283G>T)?

AlphaMissense predicts likely pathogenic (score 0.9823) — an in-silico prediction, not a clinical call.

AR p.Arg761Ser

c.2283G>T · rs2076118894 · VCV954661

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000223%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

androgen insensitivity syndrome

Computational evidence

Protein change
AlphaMissense	0.9823	likely pathogenic
REVEL	0.712	pathogenic-leaning
SaProt	LLR -11.25	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -2.8, phastCons 1
Overall
CADD	24.1	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

Grpmax group 0.000223% European (non-Finnish) · 2/895,634 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000182% 2/1,098,179 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.Arg761Ser
Coding: c.2283G>T
MANE Select: NM_000044
dbSNP: rs2076118894
Type: single nucleotide variant
Location: chrX:67717587 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 761: the nr lbd domain; the 'interaction with ccar1' region; the 'interaction with kat7' region; a β-strand; 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.Arg761fs 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
AR p.Ala766Thr 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-arg761ser (accessed [today's date]).

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