Is AR p.Arg780Gln (c.2339G>A) pathogenic?

AR p.Arg780Gln (c.2339G>A) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-19). AlphaMissense: likely pathogenic (0.6223); Ultra-rare (popmax 0.0916%, mid); Associated with partial androgen insensitivity syndrome.

What condition is associated with AR p.Arg780Gln (c.2339G>A)?

AR p.Arg780Gln (c.2339G>A) is associated with partial androgen insensitivity syndrome (ClinVar).

How common is AR p.Arg780Gln (c.2339G>A) in the general population?

AR p.Arg780Gln (c.2339G>A) is ultra-rare (popmax 0.0916%, mid) (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.Arg780Gln (c.2339G>A)?

AlphaMissense predicts likely pathogenic (score 0.6223) — an in-silico prediction, not a clinical call.

AR p.Arg780Gln

c.2339G>A · rs768366293 · VCV2442021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6223 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0916%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

partial androgen insensitivity syndrome

Computational evidence

Protein change
AlphaMissense	0.6223	likely pathogenic
REVEL	0.606	indeterminate
SaProt	LLR -8.12	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Overall
CADD	29.0	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

Grpmax group 0.0916% Middle Eastern · 4/4,369 alleles

Filtering AF 0.0312% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00132% 16/1,208,140 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0916%	1,092
Admixed American	0.00439%	22,777
Remaining individualsnot grpmax-eligible	0.0021%	47,563
South Asian	0.00176%	56,667
European (non-Finnish)	0.000894%	111,840

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.Arg780Gln
Coding: c.2339G>A
MANE Select: NM_000044
dbSNP: rs768366293
Type: single nucleotide variant
Location: chrX:67721853 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 780: the nr lbd domain; the 'interaction with ccar1' region; the 'interaction with kat7' region; a UniProt-annotated variant site (in ais); 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.Arg780Trp Pathogenic ★★ same residue
AR p.Arg780Pro Likely pathogenic ★ same residue
AR p.Arg780= Likely benign ★ 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

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-arg780gln (accessed [today's date]).

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