Is BRF1 p.Pro647= (c.1941T>C) pathogenic?

BRF1 p.Pro647= (c.1941T>C) is classified Likely benign in BRF1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-07-26). Very rare (popmax 0.000339%, nfe); Associated with BRF1-related disorder.

What condition is associated with BRF1 p.Pro647= (c.1941T>C)?

BRF1 p.Pro647= (c.1941T>C) is associated with BRF1-related disorder (ClinVar).

How common is BRF1 p.Pro647= (c.1941T>C) in the general population?

BRF1 p.Pro647= (c.1941T>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

BRF1 p.Pro647=

c.1941T>C · rs1008540253 · VCV3030943

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

BRF1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -16	GERP -2.7
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,854 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,612,406 alleles · very rare exomes 4/1,460,340 · genomes 0/152,066 · joint denominator

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.Pro647=
Coding: c.1941T>C
MANE Select: NM_001519
dbSNP: rs1008540253
Type: single nucleotide variant
Location: chr14:105211177 (GRCh38)
Structure: AlphaFold pLDDT 59.70 · 2 PDB

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

Disease context

BRF1-related disorder

Similar variants

BRF1 p.Arg512Ter Likely pathogenic ★ same condition
BRF1 p.Thr259Met Conflicting classifications of pathogenicity ★ ⚠ same condition
BRF1 c.266-7G>T Likely benign same condition
BRF1 c.915+5C>G Likely benign same condition
BRF1 p.Asp639= Likely benign same condition
BRF1 p.Thr352= Likely benign same condition
BRF1 p.Asn98fs Likely pathogenic ★ same condition
BRF1 p.Arg486fs Likely pathogenic 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-pro647 (accessed [today's date]).

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