Is AR p.Leu701Phe (c.2103G>T) pathogenic?

AR p.Leu701Phe (c.2103G>T) is classified Pathogenic in AR (ClinVar, Single submitter, 2 submitters; last evaluated 2025-06-02). AlphaMissense: likely pathogenic (0.9868); Absent from gnomAD v4.1; Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Leu701Phe (c.2103G>T)?

AR p.Leu701Phe (c.2103G>T) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Leu701Phe (c.2103G>T) in the general population?

AR p.Leu701Phe (c.2103G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AR p.Leu701Phe (c.2103G>T)?

AlphaMissense predicts likely pathogenic (score 0.9868) — an in-silico prediction, not a clinical call.

AR p.Leu701Phe

c.2103G>T · rs1555995848 · VCV458361

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9868 · 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	0.9868	likely pathogenic ✓ concordant with ClinVar
REVEL	0.842	moderately pathogenic-leaning
SaProt	LLR -13.61	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 5	GERP 1.9, phastCons 1
Overall
CADD	23.5	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.Leu701Phe
Coding: c.2103G>T
MANE Select: NM_000044
dbSNP: rs1555995848
Type: single nucleotide variant
Location: chrX:67711619 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 701: the nr lbd domain; the 'interaction with ccar1' region; the 'interaction with kat7' region; a UniProt-annotated variant site (in ais); an α-helix; 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 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
AR p.Ala871Val 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-leu701phe (accessed [today's date]).

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