Is APOBR p.Glu645Lys (c.1933G>A) pathogenic?

APOBR p.Glu645Lys (c.1933G>A) is classified Uncertain significance in APOBR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-08). AlphaMissense: likely benign (0.0959); Ultra-rare (popmax 0.0412%, amr).

How common is APOBR p.Glu645Lys (c.1933G>A) in the general population?

APOBR p.Glu645Lys (c.1933G>A) is ultra-rare (popmax 0.0412%, amr) (gnomAD).

What do computational predictors say about APOBR p.Glu645Lys (c.1933G>A)?

AlphaMissense predicts likely benign (score 0.0959) — an in-silico prediction, not a clinical call.

APOBR p.Glu645Lys

c.1933G>A · rs754869005 · VCV2383552

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0959 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0412%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0959	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -7.97	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 6.2	GERP 0.12, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 3,820 bp · p 0.27 · regional, not allelic
Overall
CADD	19.23	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 0.0412% Admixed American · 21/51,020 alleles

Filtering AF 0.0275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.00404% 63/1,559,296 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0412%	2,430
Remaining individualsnot grpmax-eligible	0.00993%	10,069
East Asian	0.00701%	14,268
European (non-Finnish)	0.00269%	37,178
African / African-American	0.00136%	73,582
South Asian	0.0012%	83,676

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: APOBR
Protein: p.Glu645Lys
Coding: c.1933G>A
MANE Select: NM_018690
dbSNP: rs754869005
Type: single nucleotide variant
Location: chr16:28496974 (GRCh38)
Gene constraint: LOEUF 0.99 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 41.14
Residue 645: the 'disordered' region

Full APOBR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOBR p.Gln807Pro Benign ★★ same type
APOBR p.Gly350= Likely benign ★★ same type
APOBR p.Ala241Gly Uncertain significance ★ ⚠ same type
APOBR p.Ala283Val Uncertain significance ★ ⚠ same type
APOBR p.Ala292Val Uncertain significance ★ ⚠ same type
APOBR p.Ala301Thr Uncertain significance ★ ⚠ same type
APOBR p.Ala33Val Uncertain significance ★ ⚠ same type
APOBR p.Ala514Asp 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/apobr-p-glu645lys (accessed [today's date]).

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