Is BRAP p.Asn284Thr (c.851A>C) pathogenic?

BRAP p.Asn284Thr (c.851A>C) is classified Uncertain significance in BRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-24). AlphaMissense: likely pathogenic (0.8866); Very rare (popmax 0.00805%, nfe).

How common is BRAP p.Asn284Thr (c.851A>C) in the general population?

BRAP p.Asn284Thr (c.851A>C) is very rare (popmax 0.00805%, nfe) (gnomAD).

What do computational predictors say about BRAP p.Asn284Thr (c.851A>C)?

AlphaMissense predicts likely pathogenic (score 0.8866) — an in-silico prediction, not a clinical call.

BRAP p.Asn284Thr

c.851A>C · rs752397283 · VCV2277906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8866 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00805%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8866	likely pathogenic
REVEL	0.411	indeterminate
SaProt	LLR -13.64	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 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 6,923 bp · p 4.4e-13 · regional, not allelic
Overall
CADD	28.0	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 0.00805% European (non-Finnish) · 95/1,180,030 alleles

Filtering AF 0.00672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00624%

Overall 0.00595% 96/1,614,024 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00805%	12,421
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Asn284Thr
Coding: c.851A>C
MANE Select: NM_006768
dbSNP: rs752397283
Type: single nucleotide variant
Location: chr12:111665684 (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-asn284thr (accessed [today's date]).

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