Is BRF1 p.Ser81Trp (c.242C>G) pathogenic?

BRF1 p.Ser81Trp (c.242C>G) is classified Uncertain significance in BRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). AlphaMissense: likely pathogenic (0.9747); Very rare (popmax 0.00334%, amr).

How common is BRF1 p.Ser81Trp (c.242C>G) in the general population?

BRF1 p.Ser81Trp (c.242C>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about BRF1 p.Ser81Trp (c.242C>G)?

AlphaMissense predicts likely pathogenic (score 0.9747) — an in-silico prediction, not a clinical call.

BRF1 p.Ser81Trp

c.242C>G · VCV3770049

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9747	likely pathogenic
REVEL	0.707	pathogenic-leaning
SaProt	LLR -16.01	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 11	GERP 1.5, phastCons 1
Overall
CADD	28.4	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 0.00334% Admixed American · 2/59,944 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,258 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.Ser81Trp
Coding: c.242C>G
MANE Select: NM_004926 · reported on NM_001519
Type: single nucleotide variant
Location: chr14:105286319 (GRCh38)
Structure: AlphaFold pLDDT 59.70 · 2 PDB
Residue 81: the 'necessary and sufficient for the association with mrna decay enzymes and mrna decay activation' region

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

Similar variants

BRF1 p.Ser81= Benign/Likely benign ★★ same residue
BRF1 p.Ser81Leu Uncertain significance ★ ⚠ same residue
BRF1 p.Pro292His Pathogenic/Likely pathogenic ★★ same type
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-ser81trp (accessed [today's date]).

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