Is AR p.Pro342Leu (c.1025C>T) pathogenic?

AR p.Pro342Leu (c.1025C>T) is classified Uncertain significance in AR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-25). AlphaMissense: likely benign (0.2143); Very rare (popmax 0.00893%, nfe); Associated with prostate cancer.

What condition is associated with AR p.Pro342Leu (c.1025C>T)?

AR p.Pro342Leu (c.1025C>T) is associated with prostate cancer (ClinVar).

How common is AR p.Pro342Leu (c.1025C>T) in the general population?

AR p.Pro342Leu (c.1025C>T) is very rare (popmax 0.00893%, nfe) (gnomAD).

What do computational predictors say about AR p.Pro342Leu (c.1025C>T)?

AlphaMissense predicts likely benign (score 0.2143) — an in-silico prediction, not a clinical call.

AR p.Pro342Leu

c.1025C>T · rs138454018 · VCV1685532

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2143 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00893%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

prostate cancer

Computational evidence

Protein change
AlphaMissense	0.2143	likely benign
REVEL	0.702	pathogenic-leaning
SaProt	LLR -7.17	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 0.96	GERP 1.2, phastCons 0.41
Overall
CADD	18.33	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 0.00893% European (non-Finnish) · 80/895,413 alleles

Filtering AF 0.00731% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00677%

Overall 0.00694% 84/1,210,972 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00893%	11,193
Remaining individualsnot grpmax-eligible	0.0063%	15,872
African / African-American	0.00174%	57,559

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.Pro342Leu
Coding: c.1025C>T
MANE Select: NM_000044
dbSNP: rs138454018
Type: single nucleotide variant
Location: chrX:67546171 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 342: the 'interaction with znf318' region; a UniProt-annotated variant site (in prostate cancer); 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.Pro342Gln Uncertain significance ★ ⚠ same residue
AR p.Pro342Ser Uncertain significance ★ ⚠ same residue
AR p.Pro342= Likely benign ★ same residue
AR p.Val867Met Pathogenic ★★ ⚠ same condition
AR p.Gln63Leu 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-pro342leu (accessed [today's date]).

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