Is AR p.Arg608Gln (c.1823G>A) pathogenic?

AR p.Arg608Gln (c.1823G>A) is classified Pathogenic/Likely pathogenic in AR (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-24). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1; Associated with AR-related disorders.

What condition is associated with AR p.Arg608Gln (c.1823G>A)?

AR p.Arg608Gln (c.1823G>A) is associated with AR-related disorders, partial androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Arg608Gln (c.1823G>A) in the general population?

AR p.Arg608Gln (c.1823G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AR p.Arg608Gln (c.1823G>A)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

AR p.Arg608Gln

c.1823G>A · rs137852573 · VCV9820

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

AR-related disorders

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic ✓ concordant with ClinVar · top 7% in AR
REVEL	0.936	strongly pathogenic-leaning
SaProt	LLR -12.52	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 12	GERP 2, phastCons 1
Overall
CADD	29.7	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.Arg608Gln
Coding: c.1823G>A
MANE Select: NM_000044
dbSNP: rs137852573
Type: single nucleotide variant
Location: chrX:67686064 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 608: the 'interaction with hipk3' region; the 'interaction with ccar1' region; a DNA-binding region; a turn; the 'interaction with lpxn' region; a UniProt-annotated variant site (in pais and breast cancer)

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

Disease context

AR-related disorders

Also linked: partial androgen insensitivity syndrome Kennedy disease androgen insensitivity syndrome

Similar variants

AR p.Arg608Ter Pathogenic ★★ same residue
AR p.Arg608= Likely benign ★ 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-arg608gln (accessed [today's date]).

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