Is BRD1 p.Leu750Phe (c.2248C>T) pathogenic?

BRD1 p.Leu750Phe (c.2248C>T) is classified Uncertain significance in BRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely benign (0.1121); Ultra-rare (popmax 0.0533%, afr).

How common is BRD1 p.Leu750Phe (c.2248C>T) in the general population?

BRD1 p.Leu750Phe (c.2248C>T) is ultra-rare (popmax 0.0533%, afr) (gnomAD).

What do computational predictors say about BRD1 p.Leu750Phe (c.2248C>T)?

AlphaMissense predicts likely benign (score 0.1121) — an in-silico prediction, not a clinical call.

BRD1 p.Leu750Phe

c.2248C>T · rs200383896 · VCV2264613

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1121 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1121	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -8.01	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 -0.18	GERP -4.6
Regional constraint	o/e 0.78	unconstrained · MANE · 17 kb · p 6.5e-07 · regional, not allelic
Overall
CADD	14.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0533% African / African-American · 40/75,082 alleles

Filtering AF 0.0401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0356%

Overall 0.00291% 47/1,614,270 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0533%	1,877
Admixed American	0.005%	20,012
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.000169%	590,023

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.Leu750Phe
Coding: c.2248C>T
MANE Select: NM_001304808
dbSNP: rs200383896
Type: single nucleotide variant
Location: chr22:49794145 (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-leu750phe (accessed [today's date]).

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