Is APOB p.Tyr720= (c.2160C>T) pathogenic?

APOB p.Tyr720= (c.2160C>T) is classified Likely benign in APOB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-30). Ultra-rare (popmax 0.03%, amr); Associated with hypercholesterolemia, autosomal dominant, type B.

What condition is associated with APOB p.Tyr720= (c.2160C>T)?

APOB p.Tyr720= (c.2160C>T) is associated with hypercholesterolemia, autosomal dominant, type B, familial hypercholesterolemia, familial hypobetalipoproteinemia 1 (ClinVar).

How common is APOB p.Tyr720= (c.2160C>T) in the general population?

APOB p.Tyr720= (c.2160C>T) is ultra-rare (popmax 0.03%, amr) (gnomAD).

APOB p.Tyr720=

c.2160C>T · rs756184175 · VCV334170

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, 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 0.14	GERP -1.4, phastCons 0.6
Overall
CADD	4.602	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% Admixed American · 18/60,000 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00403% 65/1,613,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,333
Middle Eastern	0.0164%	6,084
Finnishnot grpmax-eligible	0.0141%	7,114
South Asian	0.00329%	30,358
Remaining individualsnot grpmax-eligible	0.0032%	31,240
African / African-American	0.00267%	37,452
European (non-Finnish)	0.00254%	39,332

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.Tyr720=
Coding: c.2160C>T
MANE Select: NM_000384
dbSNP: rs756184175
Type: single nucleotide variant
Location: chr2:21026872 (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

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 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-p-tyr720 (accessed [today's date]).

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