Is AR p.Leu295Pro (c.884T>C) pathogenic?

AR p.Leu295Pro (c.884T>C) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely benign (0.1084); Very rare (popmax 0.00296%, eas).

How common is AR p.Leu295Pro (c.884T>C) in the general population?

AR p.Leu295Pro (c.884T>C) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about AR p.Leu295Pro (c.884T>C)?

AlphaMissense predicts likely benign (score 0.1084) — an in-silico prediction, not a clinical call.

AR p.Leu295Pro

c.884T>C · VCV3896317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1084 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1084	likely benign
REVEL	0.68	pathogenic-leaning
SaProt	LLR -6.83	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 3.4	GERP 2.1, phastCons 1
Overall
CADD	20.6	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 0.00296% East Asian · 1/33,829 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000455% 5/1,098,254 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,829
Remaining individualsnot grpmax-eligible	0.0021%	47,661
European (non-Finnish)	0.000335%	298,548

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.Leu295Pro
Coding: c.884T>C
MANE Select: NM_000044
Type: single nucleotide variant
Location: chrX:67546030 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 295: the 'interaction with znf318' region; the 'modulating' region

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

Similar variants

AR p.Leu295= Likely benign ★ same residue
AR c.1768+2T>C Pathogenic/Likely pathogenic ★★ same type
AR c.1769-11T>A Pathogenic ★★ same type
AR c.2450-6C>G Pathogenic ★★ same type
AR p.Ala588Pro Pathogenic/Likely pathogenic ★★ same type
AR p.Ala597Thr Pathogenic ★★ same type
AR p.Ala688Val Pathogenic/Likely pathogenic ★★ same type
AR p.Ala766Thr Pathogenic ★★ same type

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-leu295pro (accessed [today's date]).

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