Is APOB p.Lys293Glu (c.877A>G) pathogenic?

APOB p.Lys293Glu (c.877A>G) is classified Uncertain significance in APOB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-24). AlphaMissense: likely benign (0.339); Absent from gnomAD v4.1.

How common is APOB p.Lys293Glu (c.877A>G) in the general population?

APOB p.Lys293Glu (c.877A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APOB p.Lys293Glu (c.877A>G)?

AlphaMissense predicts likely benign (score 0.339) — an in-silico prediction, not a clinical call.

APOB p.Lys293Glu

c.877A>G · rs2103381922 · VCV1330894

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.339 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.339	likely benign
REVEL	0.18	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.91 · regional, not allelic
Overall
CADD	23.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APOB
Protein: p.Lys293Glu
Coding: c.877A>G
MANE Select: NM_000384
dbSNP: rs2103381922
Type: single nucleotide variant
Location: chr2:21034843 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 293: the vitellogenin domain; the 'heparin-binding' region

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

Similar variants

APOB c.1830-1G>A Pathogenic ★★ same type
APOB c.2604+1G>A Likely pathogenic ★★ same type
APOB c.537+1G>T Pathogenic/Likely pathogenic ★★ same type
APOB p.Arg1333Ter Pathogenic ★★ same type
APOB p.Arg2012Ter Pathogenic ★★ same type
APOB p.Arg2085Ter Pathogenic/Likely pathogenic ★★ same type
APOB p.Arg2513Ter Pathogenic ★★ same type
APOB p.Arg2520Ter Pathogenic/Likely pathogenic ★★ 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/apob-p-lys293glu (accessed [today's date]).

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