Is BRDT p.Lys751Arg (c.2252A>G) pathogenic?

BRDT p.Lys751Arg (c.2252A>G) is classified Uncertain significance in BRDT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.0805); Ultra-rare (popmax 0.0496%, mid).

How common is BRDT p.Lys751Arg (c.2252A>G) in the general population?

BRDT p.Lys751Arg (c.2252A>G) is ultra-rare (popmax 0.0496%, mid) (gnomAD).

What do computational predictors say about BRDT p.Lys751Arg (c.2252A>G)?

AlphaMissense predicts likely benign (score 0.0805) — an in-silico prediction, not a clinical call.

BRDT p.Lys751Arg

c.2252A>G · VCV4216118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0805 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0496%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0805	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -7.04	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 4.4	GERP -0.43, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 52 kb · p 0.018 · regional, not allelic
Overall
CADD	12.15	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 0.0496% Middle Eastern · 3/6,052 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00719%

Overall 0.00515% 83/1,611,470 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0496%	2,017
European (non-Finnish)	0.00636%	15,722
Remaining individualsnot grpmax-eligible	0.0032%	31,209
Admixed American	0.00168%	59,410
African / African-American	0.00133%	74,960
South Asian	0.00111%	90,192

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: BRDT
Protein: p.Lys751Arg
Coding: c.2252A>G
MANE Select: NM_207189
Type: single nucleotide variant
Location: chr1:91994219 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.40 · 22 PDB

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

Similar variants

BRDT p.Lys751Glu Likely benign ★ same residue
BRDT p.Gln795Ter Likely pathogenic ★ same type
BRDT p.Ala241Val Uncertain significance ★ ⚠ same type
BRDT p.Ala405Thr Uncertain significance ★ ⚠ same type
BRDT p.Ala898Gly Uncertain significance ★ ⚠ same type
BRDT p.Arg419Gln Uncertain significance ★ ⚠ same type
BRDT p.Arg422Cys Uncertain significance ★ ⚠ same type
BRDT p.Arg422Leu 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/brdt-p-lys751arg (accessed [today's date]).

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