Is AR p.Asp154Glu (c.462C>G) pathogenic?

AR p.Asp154Glu (c.462C>G) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely benign (0.0747); Very rare (popmax 0.000453%, nfe).

How common is AR p.Asp154Glu (c.462C>G) in the general population?

AR p.Asp154Glu (c.462C>G) is very rare (popmax 0.000453%, nfe) (gnomAD).

What do computational predictors say about AR p.Asp154Glu (c.462C>G)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

AR p.Asp154Glu

c.462C>G · rs140987594 · VCV2660770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000453%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -4.73	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 -3.1, phastCons 0.013
Overall
CADD	3.802	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

Grpmax group 0.000453% European (non-Finnish) · 4/883,570 alleles

Filtering AF 0.000106% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.2e-05%

Overall 0.000337% 4/1,186,798 alleles · very rare

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.Asp154Glu
Coding: c.462C>G
MANE Select: NM_000044
dbSNP: rs140987594
Type: single nucleotide variant
Location: chrX:67545608 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 154: the 'interaction with znf318' region; the 'modulating' region; the 'disordered' region

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

Similar variants

AR p.Asp154= Benign/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-asp154glu (accessed [today's date]).

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