Is BRD1 p.Pro706= (c.2118C>A) pathogenic?

BRD1 p.Pro706= (c.2118C>A) is classified Likely benign in BRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-12). Ultra-rare (popmax 0.0734%, nfe).

How common is BRD1 p.Pro706= (c.2118C>A) in the general population?

BRD1 p.Pro706= (c.2118C>A) is ultra-rare (popmax 0.0734%, nfe) (gnomAD).

BRD1 p.Pro706=

c.2118C>A · rs150570710 · VCV789249

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0734%, nfe)

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 -11	GERP -4.8
Overall
CADD	0.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0734% European (non-Finnish) · 865/1,178,714 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0677%

Overall 0.0603% 972/1,611,826 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.101%	992
European (non-Finnish)grpmax	0.0734%	1,363
Remaining individualsnot grpmax-eligible	0.0481%	2,080
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,390
African / African-American	0.00934%	10,701
Admixed American	0.00334%	29,968

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: BRD1
Protein: p.Pro706=
Coding: c.2118C>A
MANE Select: NM_001304808
dbSNP: rs150570710
Type: single nucleotide variant
Location: chr22:49794275 (GRCh38)
Gene constraint: LOEUF 0.337 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.54 · 318 PDB

Full BRD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRD1 c.1657-4C>T Likely benign ★★ same type
BRD1 p.Ala1053= Benign ★★ same type
BRD1 p.Ala730Thr Benign ★★ same type
BRD1 p.Arg1020= Benign ★★ same type
BRD1 p.Gly620= Likely benign ★★ same type
BRD1 p.Gly776Arg Benign ★★ same type
BRD1 p.Phe193= Benign ★★ same type
BRD1 p.Pro111= Benign ★★ 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/brd1-p-pro706 (accessed [today's date]).

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