Is AR p.Glu355Gln (c.1063G>C) pathogenic?

AR p.Glu355Gln (c.1063G>C) is classified Conflicting classifications of pathogenicity in AR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-16). AlphaMissense: likely benign (0.1238); Very rare (popmax 0.0057%, nfe); Associated with prostate cancer.

What condition is associated with AR p.Glu355Gln (c.1063G>C)?

AR p.Glu355Gln (c.1063G>C) is associated with prostate cancer, Kennedy disease, androgen insensitivity syndrome (ClinVar).

How common is AR p.Glu355Gln (c.1063G>C) in the general population?

AR p.Glu355Gln (c.1063G>C) is very rare (popmax 0.0057%, nfe) (gnomAD).

What do computational predictors say about AR p.Glu355Gln (c.1063G>C)?

AlphaMissense predicts likely benign (score 0.1238) — an in-silico prediction, not a clinical call.

AR p.Glu355Gln

c.1063G>C · rs367604031 · VCV1685533

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1238 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0057%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

prostate cancer

Computational evidence

Protein change
AlphaMissense	0.1238	likely benign
REVEL	0.678	pathogenic-leaning
SaProt	LLR -5.83	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.1, phastCons 1
Overall
CADD	22.3	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 0.0057% European (non-Finnish) · 51/895,099 alleles

Filtering AF 0.0044% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00398%

Overall 0.00438% 53/1,210,300 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0057%	17,551
African / African-American	0.00348%	28,736

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.Glu355Gln
Coding: c.1063G>C
MANE Select: NM_000044
dbSNP: rs367604031
Type: single nucleotide variant
Location: chrX:67546209 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 355: the 'interaction with znf318' region; the 'modulating' region

Full AR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

prostate cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Kennedy disease androgen insensitivity syndrome

Similar variants

AR p.Glu355Ter Pathogenic ★★ 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-glu355gln (accessed [today's date]).

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