Is BRAP p.Asp535Glu (c.1605C>G) pathogenic?

BRAP p.Asp535Glu (c.1605C>G) is classified Uncertain significance in BRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely pathogenic (0.9947); Very rare (popmax 8.47e-05%, nfe).

How common is BRAP p.Asp535Glu (c.1605C>G) in the general population?

BRAP p.Asp535Glu (c.1605C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about BRAP p.Asp535Glu (c.1605C>G)?

AlphaMissense predicts likely pathogenic (score 0.9947) — an in-silico prediction, not a clinical call.

BRAP p.Asp535Glu

c.1605C>G · VCV3992549

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9947 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9947	likely pathogenic · top 9% in BRAP
REVEL	0.495	indeterminate
SaProt	LLR -12.43	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9	GERP -3.7
Regional constraint	o/e 0.75	unconstrained · MANE · 14 kb · p 0.0006 · regional, not allelic
Overall
CADD	10.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,179,972 alleles

Overall 6.84e-05% 1/1,461,874 alleles · very rare

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.Asp535Glu
Coding: c.1605C>G
MANE Select: NM_006768
Type: single nucleotide variant
Location: chr12:111644373 (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.Lys451= 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

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-asp535glu (accessed [today's date]).

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