Is AR p.Ser207Arg (c.621C>G) pathogenic?

AR p.Ser207Arg (c.621C>G) is classified Benign in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-24). AlphaMissense: likely benign (0.3218); Ultra-rare (popmax 0.0644%, afr); Associated with Kennedy disease.

What condition is associated with AR p.Ser207Arg (c.621C>G)?

AR p.Ser207Arg (c.621C>G) is associated with Kennedy disease, androgen insensitivity syndrome (ClinVar).

How common is AR p.Ser207Arg (c.621C>G) in the general population?

AR p.Ser207Arg (c.621C>G) is ultra-rare (popmax 0.0644%, afr) (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.Ser207Arg (c.621C>G)?

AlphaMissense predicts likely benign (score 0.3218) — an in-silico prediction, not a clinical call.

AR p.Ser207Arg

c.621C>G · rs374549047 · VCV2946057

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3218 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0644%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Kennedy disease

Computational evidence

Protein change
AlphaMissense	0.3218	likely benign
REVEL	0.434	indeterminate
SaProt	LLR -8.01	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	20.2	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 0.0644% African / African-American · 37/57,434 alleles

Filtering AF 0.048% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0423%

Overall 0.00339% 41/1,210,611 alleles · ultra-rare exomes 17/1,097,821 · genomes 24/112,790 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0644%	1,552
Admixed American	0.00653%	15,319
Remaining individualsnot grpmax-eligible	0.0021%	47,586

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.Ser207Arg
Coding: c.621C>G
MANE Select: NM_000044
dbSNP: rs374549047
Type: single nucleotide variant
Location: chrX:67545767 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 207: the 'interaction with znf318' region; a UniProt-annotated variant site (in); the 'modulating' region; the 'disordered' 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-ser207arg (accessed [today's date]).

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