Is BRAT1 p.Phe225= (c.675C>T) pathogenic?

BRAT1 p.Phe225= (c.675C>T) is classified Benign/Likely benign in BRAT1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.34%, afr); Associated with neonatal-onset encephalopathy with rigidity and seizures.

What condition is associated with BRAT1 p.Phe225= (c.675C>T)?

BRAT1 p.Phe225= (c.675C>T) is associated with neonatal-onset encephalopathy with rigidity and seizures, neurodevelopmental disorder with cerebellar atrophy and with or without seizures (ClinVar).

How common is BRAT1 p.Phe225= (c.675C>T) in the general population?

BRAT1 p.Phe225= (c.675C>T) is low-frequency (popmax 1.34%, afr) (gnomAD).

BRAT1 p.Phe225=

c.675C>T · rs139443843 · VCV434519

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.34%, afr)

Conditions

neonatal-onset encephalopathy with rigidity and seizures

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.3	GERP -3.4
Overall
CADD	1.973	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.34% African / African-American · 1,001/74,592 alleles

Filtering AF 1.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.25%

Overall 0.0748% 1,187/1,586,200 alleles · low-frequency exomes 582/1,433,844 · genomes 605/152,356 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.34%	75
Admixed American	0.114%	876
Remaining individualsnot grpmax-eligible	0.11%	912
Middle Eastern	0.0672%	1,488
South Asian	0.00561%	17,823
European (non-Finnish)	0.00353%	28,306
East Asian	0.00226%	44,226
Finnishnot grpmax-eligible	0.0016%	62,562

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: BRAT1
Protein: p.Phe225=
Coding: c.675C>T
MANE Select: NM_152743
dbSNP: rs139443843
Type: single nucleotide variant
Location: chr7:2543718 (GRCh38)
Gene constraint: LOEUF 1.39 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.28 · 5 PDB
Residue 225: an α-helix

Full BRAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neonatal-onset encephalopathy with rigidity and seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurodevelopmental disorder with cerebellar atrophy and with or without seizures

Similar variants

BRAT1 c.1499-1G>T Pathogenic/Likely pathogenic ★★ same condition
BRAT1 c.283-1G>A Likely pathogenic ★★ same condition
BRAT1 p.Ala642Glu Likely pathogenic ★★ same condition
BRAT1 p.Arg268His Pathogenic/Likely pathogenic ★★ ⚠ same condition
BRAT1 p.Arg427Ter Likely pathogenic ★★ same condition
BRAT1 p.Arg562Ter Pathogenic/Likely pathogenic ★★ same condition
BRAT1 p.Gln196Ter Pathogenic/Likely pathogenic ★★ same condition
BRAT1 p.Gln526Ter Pathogenic ★★ 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/brat1-p-phe225 (accessed [today's date]).

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