Is APOB p.Glu29= (c.87G>A) pathogenic?

APOB p.Glu29= (c.87G>A) is classified Likely benign in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). Very rare (popmax 0.00171%, amr); Associated with familial hypercholesterolemia.

What condition is associated with APOB p.Glu29= (c.87G>A)?

APOB p.Glu29= (c.87G>A) is associated with familial hypercholesterolemia (ClinVar).

How common is APOB p.Glu29= (c.87G>A) in the general population?

APOB p.Glu29= (c.87G>A) is very rare (popmax 0.00171%, amr) (gnomAD).

APOB p.Glu29=

c.87G>A · VCV3392996

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00171%, amr)

Conditions

familial hypercholesterolemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -4.5	GERP -2.1
Overall
CADD	7.802	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00171% Admixed American · 1/58,552 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000249% 4/1,603,408 alleles · very rare exomes 4/1,451,054 · genomes 0/152,354 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00171%	58,552
European (non-Finnish)	0.000255%	391,676

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: APOB
Protein: p.Glu29=
Coding: c.87G>A
MANE Select: NM_000384
Type: single nucleotide variant
Location: chr2:21043547 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

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

Disease context

familial hypercholesterolemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APOB p.Glu29Lys Uncertain significance ★★ ⚠ same residue
APOB p.Arg2085Ter Pathogenic/Likely pathogenic ★★ same condition
APOB p.Arg3527Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
APOB p.Arg3527Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
APOB p.Ala1695Val Uncertain significance ★★ ⚠ same condition
APOB p.Ala68Thr Uncertain significance ★★ ⚠ same condition
APOB p.Arg3183Gly Uncertain significance ★★ ⚠ same condition
APOB p.Arg3311Ile Uncertain significance ★★ ⚠ same condition

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-glu29 (accessed [today's date]).

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