Is AR p.Arg386His (c.1157G>A) pathogenic?

AR p.Arg386His (c.1157G>A) is classified Benign in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-02). AlphaMissense: likely benign (0.1947); Rare (popmax 0.17%, sas); Associated with Kennedy disease.

What condition is associated with AR p.Arg386His (c.1157G>A)?

AR p.Arg386His (c.1157G>A) is associated with Kennedy disease, androgen insensitivity syndrome (ClinVar).

How common is AR p.Arg386His (c.1157G>A) in the general population?

AR p.Arg386His (c.1157G>A) is rare (popmax 0.17%, sas) (gnomAD).

How is Kennedy disease inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about AR p.Arg386His (c.1157G>A)?

AlphaMissense predicts likely benign (score 0.1947) — an in-silico prediction, not a clinical call.

AR p.Arg386His

c.1157G>A · rs555361360 · VCV2947102

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1947 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.17%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Kennedy disease

Computational evidence

Protein change
AlphaMissense	0.1947	likely benign
REVEL	0.707	pathogenic-leaning
SaProt	LLR -5.76	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	26.5	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

Grpmax group 0.17% South Asian · 94/55,278 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.132%

Overall 0.00885% 106/1,198,372 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.17%	588
Remaining individualsnot grpmax-eligible	0.0191%	5,238
African / African-American	0.00351%	28,525
European (non-Finnish)	0.000112%	889,949

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.Arg386His
Coding: c.1157G>A
MANE Select: NM_000044
dbSNP: rs555361360
Type: single nucleotide variant
Location: chrX:67546303 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 386: the 'interaction with znf318' region; the 'modulating' region

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

Disease context

Kennedy disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: androgen insensitivity syndrome

For Kennedy disease (Orphanet):

Inheritance: X-linked recessive
Onset: Adult
Prevalence: <1 / 1 000 000 (Italy)

Similar variants

AR p.Arg386Leu Likely pathogenic ★ ⚠ 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-arg386his (accessed [today's date]).

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