Is BRAT1 p.Ser604= (c.1812G>A) pathogenic?

BRAT1 p.Ser604= (c.1812G>A) is classified Likely benign in BRAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-12). Ultra-rare (popmax 0.0156%, eas); Associated with neonatal-onset encephalopathy with rigidity and seizures.

What condition is associated with BRAT1 p.Ser604= (c.1812G>A)?

BRAT1 p.Ser604= (c.1812G>A) is associated with neonatal-onset encephalopathy with rigidity and seizures (ClinVar).

How common is BRAT1 p.Ser604= (c.1812G>A) in the general population?

BRAT1 p.Ser604= (c.1812G>A) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

BRAT1 p.Ser604=

c.1812G>A · rs758363310 · VCV2739148

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

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 -20	GERP -3.3
Overall
CADD	0.043	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,872 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.001% 16/1,598,294 alleles · ultra-rare exomes 14/1,446,098 · genomes 2/152,196 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,410
Remaining individualsnot grpmax-eligible	0.0016%	62,378
African / African-American	0.00133%	74,926
South Asian	0.0011%	91,084
European (non-Finnish)	0.000509%	196,646

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.Ser604=
Coding: c.1812G>A
MANE Select: NM_152743
dbSNP: rs758363310
Type: single nucleotide variant
Location: chr7:2538723 (GRCh38)
Gene constraint: LOEUF 1.39 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.28 · 5 PDB

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

Similar variants

BRAT1 p.Ser604Leu Uncertain significance ★ ⚠ same residue
BRAT1 p.Ser604Trp Uncertain significance ★ same residue
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

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-ser604 (accessed [today's date]).

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