Is BRF2 p.Arg291Trp (c.871C>T) pathogenic?

BRF2 p.Arg291Trp (c.871C>T) is classified Uncertain significance in BRF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). AlphaMissense: likely benign (0.1967); Ultra-rare (popmax 0.0922%, sas).

How common is BRF2 p.Arg291Trp (c.871C>T) in the general population?

BRF2 p.Arg291Trp (c.871C>T) is ultra-rare (popmax 0.0922%, sas) (gnomAD).

What do computational predictors say about BRF2 p.Arg291Trp (c.871C>T)?

AlphaMissense predicts likely benign (score 0.1967) — an in-silico prediction, not a clinical call.

BRF2 p.Arg291Trp

c.871C>T · VCV3482352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1967 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0922%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1967	likely benign
REVEL	0.237	benign-leaning
SaProt	LLR -10.78	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 5,290 bp · p 0.34 · regional, not allelic
Overall
CADD	27.3	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

Grpmax group 0.0922% South Asian · 84/91,094 alleles

Filtering AF 0.0763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0704%

Overall 0.00682% 110/1,614,072 alleles · ultra-rare exomes 103/1,461,872 · genomes 7/152,200 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0922%	1,084
Remaining individualsnot grpmax-eligible	0.0064%	15,622
African / African-American	0.004%	24,979
European (non-Finnish)	0.00161%	62,108

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: BRF2
Protein: p.Arg291Trp
Coding: c.871C>T
MANE Select: NM_018310
Type: single nucleotide variant
Location: chr8:37844879 (GRCh38)

Full BRF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/brf2-p-arg291trp (accessed [today's date]).

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