Is BRF2 p.Arg313Trp (c.937C>T) pathogenic?

BRF2 p.Arg313Trp (c.937C>T) is classified Uncertain significance in BRF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.0981); Ultra-rare (popmax 0.0164%, mid).

How common is BRF2 p.Arg313Trp (c.937C>T) in the general population?

BRF2 p.Arg313Trp (c.937C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about BRF2 p.Arg313Trp (c.937C>T)?

AlphaMissense predicts likely benign (score 0.0981) — an in-silico prediction, not a clinical call.

BRF2 p.Arg313Trp

c.937C>T · rs145626361 · VCV2460904

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0981 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 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	0.0981	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.7	GERP 0.37, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 5,290 bp · p 0.34 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00851% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00795%

Overall 0.00836% 135/1,613,964 alleles · ultra-rare exomes 124/1,461,864 · genomes 11/152,100 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.0121%	8,281
European (non-Finnish)	0.01%	10,000
Remaining individualsnot grpmax-eligible	0.0048%	20,828
Finnishnot grpmax-eligible	0.00156%	63,992
African / African-American	0.00134%	74,882

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.Arg313Trp
Coding: c.937C>T
MANE Select: NM_018310
dbSNP: rs145626361
Type: single nucleotide variant
Location: chr8:37844813 (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-arg313trp (accessed [today's date]).

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