Is AR p.Ala385Ser (c.1153G>T) pathogenic?

AR p.Ala385Ser (c.1153G>T) is classified Uncertain significance in AR (ClinVar, Single submitter, 2 submitters; last evaluated 2021-07-28). AlphaMissense: likely benign (0.0746); Ultra-rare (popmax 0.0652%, amr); Associated with androgen insensitivity syndrome.

What condition is associated with AR p.Ala385Ser (c.1153G>T)?

AR p.Ala385Ser (c.1153G>T) is associated with androgen insensitivity syndrome, prostate cancer, hypospadias 1, X-linked (ClinVar).

How common is AR p.Ala385Ser (c.1153G>T) in the general population?

AR p.Ala385Ser (c.1153G>T) is ultra-rare (popmax 0.0652%, amr) (gnomAD).

What do computational predictors say about AR p.Ala385Ser (c.1153G>T)?

AlphaMissense predicts likely benign (score 0.0746) — an in-silico prediction, not a clinical call.

AR p.Ala385Ser

c.1153G>T · rs200067740 · VCV492780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0746 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0652%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

androgen insensitivity syndrome

Computational evidence

Protein change
AlphaMissense	0.0746	likely benign
REVEL	0.535	indeterminate
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -3, phastCons 0.79
Overall
CADD	15.62	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0652% Admixed American · 29/44,506 alleles

Filtering AF 0.0466% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0403%

Overall 0.00302% 36/1,193,954 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0652%	1,535
Remaining individualsnot grpmax-eligible	0.0128%	7,820
African / African-American	0.00177%	56,396

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.Ala385Ser
Coding: c.1153G>T
MANE Select: NM_000044
dbSNP: rs200067740
Type: single nucleotide variant
Location: chrX:67546299 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 385: 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: prostate cancer hypospadias 1, X-linked partial androgen insensitivity syndrome 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-ala385ser (accessed [today's date]).

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