Is BRF1 p.Gly403Ser (c.1207G>A) pathogenic?

BRF1 p.Gly403Ser (c.1207G>A) is classified Conflicting classifications of pathogenicity in BRF1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-31). AlphaMissense: likely benign (0.0686); Ultra-rare (popmax 0.0134%, amr); Associated with Inborn genetic diseases.

What condition is associated with BRF1 p.Gly403Ser (c.1207G>A)?

BRF1 p.Gly403Ser (c.1207G>A) is associated with Inborn genetic diseases, cerebellar-facial-dental syndrome (ClinVar).

How common is BRF1 p.Gly403Ser (c.1207G>A) in the general population?

BRF1 p.Gly403Ser (c.1207G>A) is ultra-rare (popmax 0.0134%, amr) (gnomAD).

What do computational predictors say about BRF1 p.Gly403Ser (c.1207G>A)?

AlphaMissense predicts likely benign (score 0.0686) — an in-silico prediction, not a clinical call.

BRF1 p.Gly403Ser

c.1207G>A · rs767304692 · VCV2688680

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0686 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0686	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.2	GERP -3.1
Overall
CADD	0.019	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 0.0134% Admixed American · 8/59,636 alleles

Filtering AF 0.00665% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00485%

Overall 0.0049% 79/1,610,844 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0134%	7,455
South Asian	0.0077%	12,992
European (non-Finnish)	0.00517%	19,337
Remaining individualsnot grpmax-eligible	0.00321%	31,136
East Asian	0.00223%	44,874

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.Gly403Ser
Coding: c.1207G>A
MANE Select: NM_004926 · reported on NM_001519
dbSNP: rs767304692
Type: single nucleotide variant
Location: chr14:105221756 (GRCh38)
Structure: AlphaFold pLDDT 59.70 · 2 PDB

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

Also linked: cerebellar-facial-dental syndrome

Similar variants

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.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

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-gly403ser (accessed [today's date]).

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