Is APOB p.Thr232= (c.696C>A) pathogenic?

APOB p.Thr232= (c.696C>A) is classified Likely benign in APOB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-05-08). Ultra-rare (popmax 0.0167%, amr); Associated with familial hypobetalipoproteinemia 1.

What condition is associated with APOB p.Thr232= (c.696C>A)?

APOB p.Thr232= (c.696C>A) is associated with familial hypobetalipoproteinemia 1, familial hypercholesterolemia, hypercholesterolemia, autosomal dominant, type B (ClinVar).

How common is APOB p.Thr232= (c.696C>A) in the general population?

APOB p.Thr232= (c.696C>A) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

APOB p.Thr232=

c.696C>A · rs199662273 · VCV1150681

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Conditions

familial hypobetalipoproteinemia 1

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	GERP 0.94
Overall
CADD	8.482	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/60,020 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.000929% 15/1,613,984 alleles · ultra-rare exomes 13/1,461,698 · genomes 2/152,286 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,002
European (non-Finnish)	0.000424%	236,003

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.Thr232=
Coding: c.696C>A
MANE Select: NM_000384
dbSNP: rs199662273
Type: single nucleotide variant
Location: chr2:21035706 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 232: the vitellogenin domain; the 'heparin-binding' region

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: familial hypercholesterolemia hypercholesterolemia, autosomal dominant, type B

Similar variants

APOB p.Thr232Asn Uncertain significance ★★ ⚠ same residue
APOB p.Thr232Pro 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-thr232 (accessed [today's date]).

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