Is BRAT1 p.Leu320Phe (c.958C>T) pathogenic?

BRAT1 p.Leu320Phe (c.958C>T) is classified Uncertain significance in BRAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-22). AlphaMissense: ambiguous (0.3877); Absent from gnomAD v4.1; Associated with neonatal-onset encephalopathy with rigidity and seizures.

What condition is associated with BRAT1 p.Leu320Phe (c.958C>T)?

BRAT1 p.Leu320Phe (c.958C>T) is associated with neonatal-onset encephalopathy with rigidity and seizures (ClinVar).

How common is BRAT1 p.Leu320Phe (c.958C>T) in the general population?

BRAT1 p.Leu320Phe (c.958C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRAT1 p.Leu320Phe (c.958C>T)?

AlphaMissense predicts ambiguous (score 0.3877) — an in-silico prediction, not a clinical call.

BRAT1 p.Leu320Phe

c.958C>T · rs1779227135 · VCV1039047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3877 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,569,164)

Conditions

neonatal-onset encephalopathy with rigidity and seizures

Computational evidence

Protein change
AlphaMissense	0.3877	ambiguous
REVEL	0.302	indeterminate
SaProt	LLR -11.94	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 16 kb · p 0.0016 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,569,164). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRAT1
Protein: p.Leu320Phe
Coding: c.958C>T
MANE Select: NM_152743
dbSNP: rs1779227135
Type: single nucleotide variant
Location: chr7:2542177 (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 320: 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-leu320phe (accessed [today's date]).

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