Is BRAT1 p.Phe703= (c.2109C>T) pathogenic?

BRAT1 p.Phe703= (c.2109C>T) is classified Likely benign in BRAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). Very rare (popmax 0.00167%, amr); Associated with neonatal-onset encephalopathy with rigidity and seizures.

What condition is associated with BRAT1 p.Phe703= (c.2109C>T)?

BRAT1 p.Phe703= (c.2109C>T) is associated with neonatal-onset encephalopathy with rigidity and seizures (ClinVar).

How common is BRAT1 p.Phe703= (c.2109C>T) in the general population?

BRAT1 p.Phe703= (c.2109C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

BRAT1 p.Phe703=

c.2109C>T · rs745775567 · VCV1571351

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 -2.9	GERP -3.1
Overall
CADD	3.805	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,032 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000992% 16/1,613,406 alleles · very rare exomes 16/1,461,086 · genomes 0/152,320 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,032
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.00119%	84,283

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.Phe703=
Coding: c.2109C>T
MANE Select: NM_152743
dbSNP: rs745775567
Type: single nucleotide variant
Location: chr7:2538426 (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 703: 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

Similar variants

BRAT1 p.Phe703Ter Pathogenic ★ 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
BRAT1 p.Gln196Ter 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-phe703 (accessed [today's date]).

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