Is BRAP p.Thr39fs (c.113dup) pathogenic?

BRAP p.Thr39fs (c.113dup) is classified Uncertain significance in BRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). Very rare (popmax 0.00949%, nfe).

How common is BRAP p.Thr39fs (c.113dup) in the general population?

BRAP p.Thr39fs (c.113dup) is very rare (popmax 0.00949%, nfe) (gnomAD).

BRAP p.Thr39fs

c.113dup · VCV4918597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00949%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP -0.42, phastCons 1
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00949% European (non-Finnish) · 112/1,179,612 alleles

Filtering AF 0.00804% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00752%

Overall 0.00781% 126/1,612,340 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00949%	10,532
African / African-American	0.00535%	18,689
Admixed American	0.00504%	19,826
Remaining individualsnot grpmax-eligible	0.00481%	20,803
South Asian	0.00331%	30,234
Finnishnot grpmax-eligible	0.00156%	64,014

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.Thr39fs
Coding: c.113dup
MANE Select: NM_006768
Type: Duplication
Location: chr12:111683276 (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.Thr39Arg Uncertain significance ★ ⚠ same residue
BRAP p.Thr39Met Uncertain significance ★ ⚠ same residue

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-thr39fs (accessed [today's date]).

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