Is CRAT p.Asp484= (c.1452C>T) pathogenic?

CRAT p.Asp484= (c.1452C>T) is classified Benign/Likely benign in CRAT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.52%, eas); Associated with neurodegeneration with brain iron accumulation 8.

What condition is associated with CRAT p.Asp484= (c.1452C>T)?

CRAT p.Asp484= (c.1452C>T) is associated with neurodegeneration with brain iron accumulation 8 (ClinVar).

How common is CRAT p.Asp484= (c.1452C>T) in the general population?

CRAT p.Asp484= (c.1452C>T) is low-frequency (popmax 1.52%, eas) (gnomAD).

CRAT p.Asp484=

c.1452C>T · rs113981850 · VCV1640077

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.52%, eas)

Conditions

neurodegeneration with brain iron accumulation 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.302	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.55, phastCons 0.99
Overall
CADD	13.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.52% East Asian · 683/44,886 alleles

Filtering AF 1.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.39%

Overall 0.0757% 1,222/1,613,828 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.52%	66
South Asian	0.438%	228
Remaining individualsnot grpmax-eligible	0.131%	762
Middle Eastern	0.0331%	3,017
African / African-American	0.0306%	3,264
European (non-Finnish)	0.00271%	36,875
Admixed American	0.00167%	60,034

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: CRAT
Protein: p.Asp484=
Coding: c.1452C>T
MANE Select: NM_000755
dbSNP: rs113981850
Type: single nucleotide variant
Location: chr9:129098025 (GRCh38)
Gene constraint: LOEUF 1.111 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.75 · 3 PDB

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

Disease context

neurodegeneration with brain iron accumulation 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRAT p.Asp484Tyr Uncertain significance ★ ⚠ same residue
CRAT p.Ala262Thr Uncertain significance ★★ ⚠ same condition
CRAT p.Arg273Trp Uncertain significance ★★ ⚠ same condition
CRAT p.Arg458His Uncertain significance ★★ ⚠ same condition
CRAT p.Arg82His Uncertain significance ★★ ⚠ same condition
CRAT p.Phe432Leu Uncertain significance ★★ ⚠ same condition
CRAT p.Ser590Leu Uncertain significance ★★ ⚠ same condition
CRAT p.Tyr117Phe 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/crat-p-asp484 (accessed [today's date]).

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