Is AR p.Pro515Ala (c.1543C>G) pathogenic?

AR p.Pro515Ala (c.1543C>G) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely benign (0.0614); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AR p.Pro515Ala (c.1543C>G)?

AR p.Pro515Ala (c.1543C>G) is associated with Inborn genetic diseases (ClinVar).

How common is AR p.Pro515Ala (c.1543C>G) in the general population?

AR p.Pro515Ala (c.1543C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AR p.Pro515Ala (c.1543C>G)?

AlphaMissense predicts likely benign (score 0.0614) — an in-silico prediction, not a clinical call.

AR p.Pro515Ala

c.1543C>G · VCV3935763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0614 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0614	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -7.02	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 0.76	GERP 0.35, phastCons 1
Overall
CADD	16.57	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AR
Protein: p.Pro515Ala
Coding: c.1543C>G
MANE Select: NM_000044
Type: single nucleotide variant
Location: chrX:67546689 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 515: the 'interaction with znf318' region; the 'modulating' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AR p.Leu446Trp Uncertain significance ★★ ⚠ same condition
AR p.Gly471= Likely benign ★★ same condition
AR p.Ala151Glu Uncertain significance ★ ⚠ same condition
AR p.Ala253Gly Uncertain significance ★ ⚠ same condition
AR p.Ala331Asp Uncertain significance ★ ⚠ same condition
AR p.Ala358Glu Uncertain significance ★ ⚠ same condition
AR p.Ala477Pro Uncertain significance ★ ⚠ same condition
AR p.Arg13Gly Uncertain significance ★ ⚠ 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-pro515ala (accessed [today's date]).

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