Is BRAT1 p.Pro799Ser (c.2395C>T) pathogenic?

BRAT1 p.Pro799Ser (c.2395C>T) is classified Uncertain significance in BRAT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-19). AlphaMissense: likely benign (0.3289); Very rare (popmax 0.00034%, nfe); Associated with neonatal-onset encephalopathy with rigidity and seizures.

What condition is associated with BRAT1 p.Pro799Ser (c.2395C>T)?

BRAT1 p.Pro799Ser (c.2395C>T) is associated with neonatal-onset encephalopathy with rigidity and seizures (ClinVar).

How common is BRAT1 p.Pro799Ser (c.2395C>T) in the general population?

BRAT1 p.Pro799Ser (c.2395C>T) is very rare (popmax 0.00034%, nfe) (gnomAD).

What do computational predictors say about BRAT1 p.Pro799Ser (c.2395C>T)?

AlphaMissense predicts likely benign (score 0.3289) — an in-silico prediction, not a clinical call.

BRAT1 p.Pro799Ser

c.2395C>T · rs762276921 · VCV540173

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3289 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neonatal-onset encephalopathy with rigidity and seizures

Computational evidence

Protein change
AlphaMissense	0.3289	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -5.49	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 7.4	GERP -1, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 16 kb · p 0.0016 · regional, not allelic
Overall
CADD	22.9	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 0.00034% European (non-Finnish) · 4/1,175,828 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000275% 4/1,455,140 alleles · very 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: BRAT1
Protein: p.Pro799Ser
Coding: c.2395C>T
MANE Select: NM_152743
dbSNP: rs762276921
Type: single nucleotide variant
Location: chr7:2538140 (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 799: 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 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-pro799ser (accessed [today's date]).

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