Is AR p.Ser328Cys (c.983C>G) pathogenic?

AR p.Ser328Cys (c.983C>G) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-21). AlphaMissense: likely benign (0.1052); Absent from gnomAD v4.1; Associated with Kennedy disease.

What condition is associated with AR p.Ser328Cys (c.983C>G)?

AR p.Ser328Cys (c.983C>G) is associated with Kennedy disease, androgen insensitivity syndrome (ClinVar).

How common is AR p.Ser328Cys (c.983C>G) in the general population?

AR p.Ser328Cys (c.983C>G) is absent from gnomAD v4.1 (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.Ser328Cys (c.983C>G)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

AR p.Ser328Cys

c.983C>G · rs1929717720 · VCV1492147

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Kennedy disease

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.402	indeterminate
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	20.3	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

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.Ser328Cys
Coding: c.983C>G
MANE Select: NM_000044
dbSNP: rs1929717720
Type: single nucleotide variant
Location: chrX:67546129 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 328: 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 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-ser328cys (accessed [today's date]).

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