Is AR p.Val478Ala (c.1433T>C) pathogenic?

AR p.Val478Ala (c.1433T>C) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-14). AlphaMissense: likely benign (0.0963); Ultra-rare (popmax 0.0214%, amr); Associated with Inborn genetic diseases.

What condition is associated with AR p.Val478Ala (c.1433T>C)?

AR p.Val478Ala (c.1433T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AR p.Val478Ala (c.1433T>C) in the general population?

AR p.Val478Ala (c.1433T>C) is ultra-rare (popmax 0.0214%, amr) (gnomAD).

What do computational predictors say about AR p.Val478Ala (c.1433T>C)?

AlphaMissense predicts likely benign (score 0.0963) — an in-silico prediction, not a clinical call.

AR p.Val478Ala

c.1433T>C · VCV4583405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0963 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0963	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -4.60	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 2.2	GERP -0.23, phastCons 0.63
Overall
CADD	12.07	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 0.0214% Admixed American · 8/37,310 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00772%

Overall 0.000714% 8/1,119,869 alleles · ultra-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.Val478Ala
Coding: c.1433T>C
MANE Select: NM_000044
Type: single nucleotide variant
Location: chrX:67546579 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 478: the 'interaction with znf318' region; 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.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
AR p.Ala358Glu Uncertain significance ★ ⚠ same condition
AR p.Ala477Pro Uncertain significance ★ ⚠ same condition
AR p.Arg13Gly 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-val478ala (accessed [today's date]).

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