Is BRF1 p.Ala296Val (c.887C>T) pathogenic?

BRF1 p.Ala296Val (c.887C>T) is classified Uncertain significance in BRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.1752); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BRF1 p.Ala296Val (c.887C>T)?

BRF1 p.Ala296Val (c.887C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BRF1 p.Ala296Val (c.887C>T) in the general population?

BRF1 p.Ala296Val (c.887C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRF1 p.Ala296Val (c.887C>T)?

AlphaMissense predicts likely benign (score 0.1752) — an in-silico prediction, not a clinical call.

BRF1 p.Ala296Val

c.887C>T · VCV4216153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1752 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1752	likely benign
REVEL	0.402	indeterminate
SaProt	LLR -11.20	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.93 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRF1
Protein: p.Ala296Val
Coding: c.887C>T
MANE Select: NM_004926 · reported on NM_001519
Type: single nucleotide variant
Location: chr14:105226662 (GRCh38)
Structure: AlphaFold pLDDT 59.70 · 2 PDB
Residue 296: the 'necessary for mrna decay activation' region; the 'disordered' region

Full BRF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRF1 p.Ala565Ser Uncertain significance ★★ ⚠ same condition
BRF1 p.Arg213Lys Uncertain significance ★★ ⚠ same condition
BRF1 p.Arg216Gln Uncertain significance ★★ ⚠ same condition
BRF1 p.Arg261Gln Uncertain significance ★★ ⚠ same condition
BRF1 p.Arg302Trp Uncertain significance ★★ ⚠ same condition
BRF1 p.Gly402Ser Uncertain significance ★★ ⚠ same condition
BRF1 p.Leu138Pro Uncertain significance ★★ ⚠ same condition
BRF1 p.Thr295Ala Uncertain significance ★★ ⚠ 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/brf1-p-ala296val (accessed [today's date]).

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