Is BRF1 p.Pro292Arg (c.875C>G) pathogenic?

BRF1 p.Pro292Arg (c.875C>G) is classified Likely pathogenic in BRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-26). AlphaMissense: likely pathogenic (0.9903); Very rare (popmax 0.00223%, eas).

How common is BRF1 p.Pro292Arg (c.875C>G) in the general population?

BRF1 p.Pro292Arg (c.875C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BRF1 p.Pro292Arg (c.875C>G)?

AlphaMissense predicts likely pathogenic (score 0.9903) — an in-silico prediction, not a clinical call.

BRF1 p.Pro292Arg

c.875C>G · rs606231450 · VCV1098378

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9903	likely pathogenic ✓ concordant with ClinVar
REVEL	0.738	pathogenic-leaning
SaProt	LLR -16.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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	24.8	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

Grpmax group 0.00223% East Asian · 1/44,876 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.0013% 19/1,461,222 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
European (non-Finnish)	0.00144%	69,413
South Asian	0.0011%	91,084

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.Pro292Arg
Coding: c.875C>G
MANE Select: NM_004926 · reported on NM_001519
dbSNP: rs606231450
Type: single nucleotide variant
Location: chr14:105226674 (GRCh38)
Structure: AlphaFold pLDDT 59.70 · 2 PDB
Residue 292: the 'necessary for mrna decay activation' region; the 'disordered' region

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

Similar variants

BRF1 p.Pro292His Pathogenic/Likely pathogenic ★★ same residue
BRF1 p.Pro292Leu Uncertain significance ★ ⚠ same residue
BRF1 p.Pro292= Likely benign ★ same residue
BRF1 p.Ser226Leu Pathogenic/Likely pathogenic ★★ same type
BRF1 p.Ala565Ser Uncertain significance ★★ ⚠ same type
BRF1 p.Arg213Lys Uncertain significance ★★ ⚠ same type
BRF1 p.Arg216Gln Uncertain significance ★★ ⚠ same type
BRF1 p.Arg261Gln Uncertain significance ★★ ⚠ same type

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-pro292arg (accessed [today's date]).

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