Is AR p.Arg618Trp (c.1852C>T) pathogenic?

AR p.Arg618Trp (c.1852C>T) is classified Likely pathogenic in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely pathogenic (0.9955); Very rare (popmax 0.00218%, amr); Associated with male infertility.

What condition is associated with AR p.Arg618Trp (c.1852C>T)?

AR p.Arg618Trp (c.1852C>T) is associated with male infertility (ClinVar).

How common is AR p.Arg618Trp (c.1852C>T) in the general population?

AR p.Arg618Trp (c.1852C>T) is very rare (popmax 0.00218%, amr) (gnomAD).

What do computational predictors say about AR p.Arg618Trp (c.1852C>T)?

AlphaMissense predicts likely pathogenic (score 0.9955) — an in-silico prediction, not a clinical call.

AR p.Arg618Trp

c.1852C>T · rs1218564193 · VCV3061773

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9955 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00218%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

male infertility

Computational evidence

Protein change
AlphaMissense	0.9955	likely pathogenic ✓ concordant with ClinVar
REVEL	0.892	moderately pathogenic-leaning
SaProt	LLR -14.56	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 2, phastCons 1
Overall
CADD	27.2	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 0.00218% Admixed American · 1/45,969 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000273% 3/1,097,309 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00218%	45,969
European (non-Finnish)	0.000223%	447,439

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.Arg618Trp
Coding: c.1852C>T
MANE Select: NM_000044
dbSNP: rs1218564193
Type: single nucleotide variant
Location: chrX:67686093 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 618: the 'interaction with hipk3' region; the 'interaction with ccar1' region; a DNA-binding region; an α-helix; the 'interaction with lpxn' region; a UniProt-annotated variant site (in ais and pais; loss of dna-binding activity)

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

Disease context

male infertility — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AR p.Arg618= Benign ★ same residue
AR p.Arg856His Pathogenic/Likely pathogenic ★★ same condition
AR p.Asn757Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
AR p.Tyr408Cys Uncertain significance ★★ ⚠ same condition
AR p.Arg787Gln Likely pathogenic ★ same condition
AR p.Asp829Val Pathogenic ★ same condition
AR p.Cys687Arg Pathogenic ★ ⚠ same condition
AR p.Ala159Thr Conflicting classifications of pathogenicity ★ 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-arg618trp (accessed [today's date]).

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