Is BRF1 p.Thr606= (c.1818G>A) pathogenic?

BRF1 p.Thr606= (c.1818G>A) is classified Likely benign in BRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). Very rare (popmax 0.00667%, afr).

How common is BRF1 p.Thr606= (c.1818G>A) in the general population?

BRF1 p.Thr606= (c.1818G>A) is very rare (popmax 0.00667%, afr) (gnomAD).

BRF1 p.Thr606=

c.1818G>A · VCV4534290

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

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 -3.4	GERP -2.8
Overall
CADD	1.756	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,940 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00595% 96/1,612,672 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0127%	7,899
African / African-Americangrpmax	0.00667%	14,988
European (non-Finnish)	0.00653%	15,321
Remaining individualsnot grpmax-eligible	0.00641%	15,611
Admixed American	0.00334%	29,983

Finnish 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.Thr606=
Coding: c.1818G>A
MANE Select: NM_004926 · reported on NM_001519
Type: single nucleotide variant
Location: chr14:105212119 (GRCh38)
Structure: AlphaFold pLDDT 59.70 · 2 PDB

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

Similar variants

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
BRF1 p.Arg302Trp Uncertain significance ★★ ⚠ same type
BRF1 p.Gly402Ser 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-thr606 (accessed [today's date]).

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