Is BRF1 p.His201Pro (c.602A>C) pathogenic?

BRF1 p.His201Pro (c.602A>C) is classified Uncertain significance in BRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.859); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BRF1 p.His201Pro (c.602A>C)?

BRF1 p.His201Pro (c.602A>C) is associated with Inborn genetic diseases (ClinVar).

How common is BRF1 p.His201Pro (c.602A>C) in the general population?

BRF1 p.His201Pro (c.602A>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about BRF1 p.His201Pro (c.602A>C)?

AlphaMissense predicts likely pathogenic (score 0.859) — an in-silico prediction, not a clinical call.

BRF1 p.His201Pro

c.602A>C · VCV4599039

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.859	likely pathogenic
REVEL	0.219	benign-leaning
SaProt	LLR -13.14	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Overall
CADD	25.1	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 0.000424% European (non-Finnish) · 5/1,179,924 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000411% 6/1,460,466 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)grpmax	0.000424%	235,985

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.His201Pro
Coding: c.602A>C
MANE Select: NM_004926 · reported on NM_001519
Type: single nucleotide variant
Location: chr14:105241357 (GRCh38)
Structure: AlphaFold pLDDT 59.70 · 2 PDB
Residue 201: the 'necessary for mrna decay activation' 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.His201= 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-his201pro (accessed [today's date]).

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