Is AR p.Pro392Arg (c.1175C>G) pathogenic?

AR p.Pro392Arg (c.1175C>G) is classified Conflicting classifications of pathogenicity in AR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-08-04). AlphaMissense: likely benign (0.1934); Very rare (popmax 0.00607%, eas); Associated with prostate cancer.

What condition is associated with AR p.Pro392Arg (c.1175C>G)?

AR p.Pro392Arg (c.1175C>G) is associated with prostate cancer (ClinVar).

How common is AR p.Pro392Arg (c.1175C>G) in the general population?

AR p.Pro392Arg (c.1175C>G) is very rare (popmax 0.00607%, eas) (gnomAD).

What do computational predictors say about AR p.Pro392Arg (c.1175C>G)?

AlphaMissense predicts likely benign (score 0.1934) — an in-silico prediction, not a clinical call.

AR p.Pro392Arg

c.1175C>G · rs773996740 · VCV1685534

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1934 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00607%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

prostate cancer

Computational evidence

Protein change
AlphaMissense	0.1934	likely benign
REVEL	0.841	moderately pathogenic-leaning
SaProt	LLR -8.23	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 5.8	GERP 1.3, phastCons 1
Overall
CADD	22.2	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 0.00607% East Asian · 2/32,948 alleles

Filtering AF 0.00101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000376%

Overall 0.000753% 9/1,195,565 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00607%	16,474
African / African-American	0.00175%	57,236
European (non-Finnish)	0.000675%	148,051

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.Pro392Arg
Coding: c.1175C>G
MANE Select: NM_000044
dbSNP: rs773996740
Type: single nucleotide variant
Location: chrX:67546321 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 392: the 'interaction with znf318' region; a UniProt-annotated variant site (in ais); 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

Similar variants

AR p.Pro392Leu Uncertain significance ★ ⚠ same residue
AR p.Pro392Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
AR p.Val867Met Pathogenic ★★ ⚠ same condition
AR p.Gln63Leu Uncertain significance ★★ ⚠ same condition
AR p.Pro342Leu Uncertain significance ★★ ⚠ same condition
AR p.Ser176Arg Benign/Likely benign ★★ ⚠ same condition
AR p.Ala403Val Pathogenic ★ same condition
AR p.Asn728Lys 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-pro392arg (accessed [today's date]).

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