Is AR p.Leu249= (c.747G>A) pathogenic?

AR p.Leu249= (c.747G>A) is classified Benign in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). Very rare (popmax 0.00351%, sas); Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Leu249= (c.747G>A)?

AR p.Leu249= (c.747G>A) is associated with androgen insensitivity syndrome, Kennedy disease (ClinVar).

How common is AR p.Leu249= (c.747G>A) in the general population?

AR p.Leu249= (c.747G>A) is very rare (popmax 0.00351%, sas) (gnomAD).

AR p.Leu249=

c.747G>A · rs745476348 · VCV2184701

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00351%, sas)

Conditions

androgen insensitivity syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.62, phastCons 1
Overall
CADD	10.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00351% South Asian · 2/57,028 alleles

Filtering AF 0.000582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.00066% 8/1,212,228 alleles · very rare exomes 8/1,098,198 · genomes 0/114,030 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00351%	28,514
European (non-Finnish)	0.00067%	149,266

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.Leu249=
Coding: c.747G>A
MANE Select: NM_000044
dbSNP: rs745476348
Type: single nucleotide variant
Location: chrX:67545893 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 249: the 'interaction with znf318' region; the 'modulating' 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-leu249 (accessed [today's date]).

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