Is AR p.Ile673Val (c.2017A>G) pathogenic?

AR p.Ile673Val (c.2017A>G) is classified Conflicting classifications of pathogenicity in AR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-01). AlphaMissense: likely benign (0.0819); Ultra-rare (popmax 0.035%, afr); Associated with Kennedy disease.

What condition is associated with AR p.Ile673Val (c.2017A>G)?

AR p.Ile673Val (c.2017A>G) is associated with Kennedy disease, androgen insensitivity syndrome (ClinVar).

How common is AR p.Ile673Val (c.2017A>G) in the general population?

AR p.Ile673Val (c.2017A>G) is ultra-rare (popmax 0.035%, 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.Ile673Val (c.2017A>G)?

AlphaMissense predicts likely benign (score 0.0819) — an in-silico prediction, not a clinical call.

AR p.Ile673Val

c.2017A>G · rs146618994 · VCV2923898

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0819 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Kennedy disease

Computational evidence

Protein change
AlphaMissense	0.0819	likely benign
REVEL	0.272	benign-leaning
SaProt	LLR -4.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.7, phastCons 1
Overall
CADD	20.8	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 0.035% African / African-American · 20/57,145 alleles

Filtering AF 0.0232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0194%

Overall 0.00182% 22/1,210,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.035%	2,857
Admixed American	0.00437%	22,886

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.Ile673Val
Coding: c.2017A>G
MANE Select: NM_000044
dbSNP: rs146618994
Type: single nucleotide variant
Location: chrX:67711533 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 673: the nr lbd domain; a UniProt-annotated variant site (in prostate cancer); the 'interaction with ccar1' region; the 'interaction with kat7' region; an α-helix; the 'interaction with lpxn' 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-ile673val (accessed [today's date]).

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