Is BRAP p.Ala565Thr (c.1693G>A) pathogenic?

BRAP p.Ala565Thr (c.1693G>A) is classified Uncertain significance in BRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.1948); Ultra-rare (popmax 0.0493%, mid).

How common is BRAP p.Ala565Thr (c.1693G>A) in the general population?

BRAP p.Ala565Thr (c.1693G>A) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about BRAP p.Ala565Thr (c.1693G>A)?

AlphaMissense predicts likely benign (score 0.1948) — an in-silico prediction, not a clinical call.

BRAP p.Ala565Thr

c.1693G>A · VCV3825235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1948 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1948	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -6.70	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 0.41	GERP -5.6, phastCons 0.026
Regional constraint	o/e 1.21	unconstrained · MANE · 141 bp · p 0.089 · regional, not allelic
Overall
CADD	16.44	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00223% 36/1,613,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
South Asian	0.00988%	10,120
Admixed American	0.00834%	11,997
Remaining individualsnot grpmax-eligible	0.0032%	31,245
European (non-Finnish)	0.00144%	69,414

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.Ala565Thr
Coding: c.1693G>A
MANE Select: NM_006768
Type: single nucleotide variant
Location: chr12:111644285 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.92
Residue 565: the 'disordered' region

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-ala565thr (accessed [today's date]).

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