Is BRAP p.Lys451= (c.1353G>A) pathogenic?

BRAP p.Lys451= (c.1353G>A) is classified Benign in BRAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-05-08). Common (popmax 5.3%, afr) — too common for a highly-penetrant pathogenic allele.

BRAP p.Lys451=

Q: How common is BRAP p.Lys451= (c.1353G>A) in the general population?

BRAP p.Lys451= (c.1353G>A) is common (popmax 5.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1353G>A · rs61739319 · VCV768584

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.3%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.083	GERP -3.4, phastCons 0.8
Overall
CADD	4.732	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.3% African / African-American · 3,974/74,956 alleles

Filtering AF 5.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.11%

Overall 0.288% 4,649/1,611,846 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.3%	19
Remaining individualsnot grpmax-eligible	0.437%	229
Middle Eastern	0.413%	242
Admixed American	0.379%	264
South Asian	0.0132%	7,569
European (non-Finnish)	0.0117%	8,540

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: BRAP
Protein: p.Lys451=
Coding: c.1353G>A
MANE Select: NM_006768
dbSNP: rs61739319
Type: single nucleotide variant
Location: chr12:111650001 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.92

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

Similar variants

BRAP p.Ala42= Benign ★★ same type
BRAP p.Gly250= Benign ★★ same type
BRAP p.Ile193= Benign ★★ same type
BRAP p.Ala100Val Uncertain significance ★ ⚠ same type
BRAP p.Ala379Val Uncertain significance ★ same type
BRAP p.Ala403Ser Uncertain significance ★ ⚠ same type
BRAP p.Ala481Gly Uncertain significance ★ ⚠ same type
BRAP p.Ala565Thr 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/brap-p-lys451 (accessed [today's date]).

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