Is APOB c.82+2T>C pathogenic?

APOB c.82+2T>C is classified Likely pathogenic in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-05). Absent from gnomAD v4.1; Associated with familial hypobetalipoproteinemia 1.

What condition is associated with APOB c.82+2T>C?

APOB c.82+2T>C is associated with familial hypobetalipoproteinemia 1, hypercholesterolemia, autosomal dominant, type B (ClinVar).

How common is APOB c.82+2T>C in the general population?

APOB c.82+2T>C is absent from gnomAD v4.1 (gnomAD).

APOB c.82+2T>C

rs1558269982 · VCV2134447

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,508,386)

Conditions

familial hypobetalipoproteinemia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.94	donor loss · deltas
Pangolin	Δ0.79	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 0.74, phastCons 1
Non-coding constraint	Z 2.02	1 kb window · o/e 0.83 · regional · uncalibrated
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,508,386). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: APOB
Coding: c.82+2T>C
MANE Select: NM_000384
dbSNP: rs1558269982
Type: single nucleotide variant
Location: chr2:21043862 (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 hypobetalipoproteinemia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypercholesterolemia, autosomal dominant, type B

Similar variants

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
APOB p.Arg2513Ter Pathogenic ★★ same condition
APOB p.Arg2520Ter 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-c-82-plus-2t-c (accessed [today's date]).

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