Is BRF1 p.Ser293Trp (c.878C>G) pathogenic?

BRF1 p.Ser293Trp (c.878C>G) is classified Uncertain significance in BRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely pathogenic (0.9889); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with BRF1 p.Ser293Trp (c.878C>G)?

BRF1 p.Ser293Trp (c.878C>G) is associated with Inborn genetic diseases (ClinVar).

How common is BRF1 p.Ser293Trp (c.878C>G) in the general population?

BRF1 p.Ser293Trp (c.878C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about BRF1 p.Ser293Trp (c.878C>G)?

AlphaMissense predicts likely pathogenic (score 0.9889) — an in-silico prediction, not a clinical call.

BRF1 p.Ser293Trp

c.878C>G · rs773768880 · VCV2240805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9889 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9889	likely pathogenic
REVEL	0.294	indeterminate
SaProt	LLR -16.41	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0011% South Asian · 1/91,084 alleles

Overall 0.000657% 1/152,212 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: BRF1
Protein: p.Ser293Trp
Coding: c.878C>G
MANE Select: NM_004926 · reported on NM_001519
dbSNP: rs773768880
Type: single nucleotide variant
Location: chr14:105226671 (GRCh38)
Structure: AlphaFold pLDDT 59.70 · 2 PDB
Residue 293: 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.Ser293= Likely benign ★★ same residue
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

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-ser293trp (accessed [today's date]).

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