Is AR p.Ser343= (c.1029T>C) pathogenic?

AR p.Ser343= (c.1029T>C) is classified Benign in AR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-19). Low-frequency (popmax 1.57%, afr); Associated with Kennedy disease.

What condition is associated with AR p.Ser343= (c.1029T>C)?

AR p.Ser343= (c.1029T>C) is associated with Kennedy disease, androgen insensitivity syndrome (ClinVar).

How common is AR p.Ser343= (c.1029T>C) in the general population?

AR p.Ser343= (c.1029T>C) is low-frequency (popmax 1.57%, afr) (gnomAD).

How is Kennedy disease inherited?

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

AR p.Ser343=

c.1029T>C · rs113983339 · VCV1336058

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.57%, afr)

Conditions

Kennedy disease

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 1.3	GERP 0.36, phastCons 0.8
Overall
CADD	8.284	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.57% African / African-American · 903/57,641 alleles

Filtering AF 1.48% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.45%

Overall 0.0837% 1,014/1,211,082 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.57%	64
Remaining individualsnot grpmax-eligible	0.126%	794
Admixed American	0.0868%	1,152
Middle Eastern	0.0459%	2,178
South Asian	0.00703%	14,226
European (non-Finnish)	0.000558%	179,081

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.Ser343=
Coding: c.1029T>C
MANE Select: NM_000044
dbSNP: rs113983339
Type: single nucleotide variant
Location: chrX:67546175 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 343: 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.Ser343Phe Uncertain significance ★ ⚠ 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-ser343 (accessed [today's date]).

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