Is BRAP p.Glu310Lys (c.928G>A) pathogenic?

BRAP p.Glu310Lys (c.928G>A) is classified Uncertain significance in BRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely pathogenic (0.8323); Very rare (popmax 0.0034%, nfe).

How common is BRAP p.Glu310Lys (c.928G>A) in the general population?

BRAP p.Glu310Lys (c.928G>A) is very rare (popmax 0.0034%, nfe) (gnomAD).

What do computational predictors say about BRAP p.Glu310Lys (c.928G>A)?

AlphaMissense predicts likely pathogenic (score 0.8323) — an in-silico prediction, not a clinical call.

BRAP p.Glu310Lys

c.928G>A · rs747386868 · VCV2490648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8323 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0034%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8323	likely pathogenic
REVEL	0.246	benign-leaning
SaProt	LLR -9.74	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 6,923 bp · p 4.4e-13 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0034% European (non-Finnish) · 40/1,176,942 alleles

Filtering AF 0.00256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00226%

Overall 0.00282% 41/1,455,826 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0034%	29,424
Remaining individualsnot grpmax-eligible	0.00161%	62,126

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.Glu310Lys
Coding: c.928G>A
MANE Select: NM_006768
dbSNP: rs747386868
Type: single nucleotide variant
Location: chr12:111660644 (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-glu310lys (accessed [today's date]).

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