Is BRF1 p.Pro183= (c.549G>A) pathogenic?

BRF1 p.Pro183= (c.549G>A) is classified Benign/Likely benign in BRF1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-01). Rare (popmax 0.55%, sas); Associated with cerebellar-facial-dental syndrome.

What condition is associated with BRF1 p.Pro183= (c.549G>A)?

BRF1 p.Pro183= (c.549G>A) is associated with cerebellar-facial-dental syndrome (ClinVar).

How common is BRF1 p.Pro183= (c.549G>A) in the general population?

BRF1 p.Pro183= (c.549G>A) is rare (popmax 0.55%, sas) (gnomAD).

BRF1 p.Pro183=

c.549G>A · rs144658695 · VCV770430

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.55%, sas)

Conditions

cerebellar-facial-dental syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.318	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.9	GERP -2.9
Overall
CADD	0.345	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.55% South Asian · 501/91,092 alleles

Filtering AF 0.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.494%

Overall 0.375% 6,046/1,611,592 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.75%	57
South Asiangrpmax	0.55%	182
European (non-Finnish)	0.436%	229
Remaining individualsnot grpmax-eligible	0.328%	305
Finnishnot grpmax-eligible	0.114%	881
African / African-American	0.0786%	1,272
Admixed American	0.0683%	1,464
Middle Eastern	0.0495%	2,019
East Asian	0.00891%	11,220

Amish 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.Pro183=
Coding: c.549G>A
MANE Select: NM_004926 · reported on NM_001519
dbSNP: rs144658695
Type: single nucleotide variant
Location: chr14:105241410 (GRCh38)
Structure: AlphaFold pLDDT 59.70 · 2 PDB

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

Disease context

cerebellar-facial-dental syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BTBD6 p.Pro183Ser Uncertain significance ★ same residue
BRF1 p.Pro292His Pathogenic/Likely pathogenic ★★ same condition
BRF1 p.Ser226Leu Pathogenic/Likely pathogenic ★★ same condition
BRF1 p.Ala565Ser Uncertain significance ★★ ⚠ same condition
BRF1 p.Gly402Ser Uncertain significance ★★ ⚠ same condition
BRF1 c.1378-12G>C Uncertain significance ★ same condition
BRF1 p.Ala396Thr Uncertain significance ★ ⚠ same condition
BRF1 p.Arg572Gly Conflicting classifications of pathogenicity ★ ⚠ 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-pro183 (accessed [today's date]).

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