Is APOB p.Ala2114= (c.6342C>T) pathogenic?

APOB p.Ala2114= (c.6342C>T) is classified Conflicting classifications of pathogenicity in APOB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-10-04). Very rare (popmax 0.00334%, amr); Associated with hypercholesterolemia, autosomal dominant, type B.

What condition is associated with APOB p.Ala2114= (c.6342C>T)?

APOB p.Ala2114= (c.6342C>T) is associated with hypercholesterolemia, autosomal dominant, type B, familial hypercholesterolemia, familial hypobetalipoproteinemia 1 (ClinVar).

How common is APOB p.Ala2114= (c.6342C>T) in the general population?

APOB p.Ala2114= (c.6342C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

APOB p.Ala2114=

c.6342C>T · rs768164831 · VCV334131

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

hypercholesterolemia, autosomal dominant, type B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -1.3, phastCons 1
Overall
CADD	5.681	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,870 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,457,802 alleles · very rare

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.Ala2114=
Coding: c.6342C>T
MANE Select: NM_000384
dbSNP: rs768164831
Type: single nucleotide variant
Location: chr2:21010526 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2114: the 'heparin-binding' region

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

Disease context

hypercholesterolemia, autosomal dominant, type B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypercholesterolemia familial hypobetalipoproteinemia 1

Similar variants

APOB p.Ala2114Ser Uncertain significance ★ ⚠ same residue
APOB p.Ala2114Val Uncertain significance ★ ⚠ same residue
APOB c.1830-1G>A Pathogenic ★★ same condition
APOB c.2604+1G>A Likely pathogenic ★★ same condition
APOB c.537+1G>T Pathogenic/Likely pathogenic ★★ same condition
APOB p.Arg1333Ter Pathogenic ★★ same condition
APOB p.Arg2012Ter Pathogenic ★★ same condition
APOB p.Arg2085Ter Pathogenic/Likely pathogenic ★★ 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-ala2114 (accessed [today's date]).

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