Is AR p.Pro342Gln (c.1025C>A) pathogenic?

AR p.Pro342Gln (c.1025C>A) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). AlphaMissense: likely benign (0.1674); Ultra-rare (popmax 0.0399%, afr); Associated with Inborn genetic diseases.

What condition is associated with AR p.Pro342Gln (c.1025C>A)?

AR p.Pro342Gln (c.1025C>A) is associated with Inborn genetic diseases (ClinVar).

How common is AR p.Pro342Gln (c.1025C>A) in the general population?

AR p.Pro342Gln (c.1025C>A) is ultra-rare (popmax 0.0399%, afr) (gnomAD).

What do computational predictors say about AR p.Pro342Gln (c.1025C>A)?

AlphaMissense predicts likely benign (score 0.1674) — an in-silico prediction, not a clinical call.

AR p.Pro342Gln

c.1025C>A · rs138454018 · VCV2515300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1674 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0399%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1674	likely benign
REVEL	0.649	pathogenic-leaning
SaProt	LLR -7.41	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	17.7	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 0.0399% African / African-American · 23/57,626 alleles

Filtering AF 0.0273% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.00231% 28/1,211,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0399%	2,505
Remaining individualsnot grpmax-eligible	0.0063%	15,878
Admixed American	0.00434%	23,023

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.Pro342Gln
Coding: c.1025C>A
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

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

Similar variants

AR p.Pro342Ser Uncertain significance ★ ⚠ same residue
AR p.Pro342Leu Uncertain significance ★★ ⚠ same residue
AR p.Pro342= Likely benign ★ same residue
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

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-pro342gln (accessed [today's date]).

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