Is AR p.Ile604Phe (c.1810A>T) pathogenic?

AR p.Ile604Phe (c.1810A>T) is classified Likely pathogenic in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-08). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1; Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Ile604Phe (c.1810A>T)?

AR p.Ile604Phe (c.1810A>T) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Ile604Phe (c.1810A>T) in the general population?

AR p.Ile604Phe (c.1810A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AR p.Ile604Phe (c.1810A>T)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

AR p.Ile604Phe

c.1810A>T · VCV4783657

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

androgen insensitivity syndrome

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic ✓ concordant with ClinVar · top 4% in AR
REVEL	0.893	moderately pathogenic-leaning
SaProt	LLR -13.56	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 11	GERP 2, phastCons 1
Overall
CADD	26.9	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.Ile604Phe
Coding: c.1810A>T
MANE Select: NM_000044
Type: single nucleotide variant
Location: chrX:67686051 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 604: the 'interaction with hipk3' region; the 'interaction with ccar1' region; a DNA-binding region; 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.Ile604= 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
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-ile604phe (accessed [today's date]).

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