Is APOB p.Phe1455= (c.4365C>T) pathogenic?

APOB p.Phe1455= (c.4365C>T) is classified Benign/Likely benign in APOB (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-19). Common (popmax 6.77%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Phe1455= (c.4365C>T)?

APOB p.Phe1455= (c.4365C>T) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

APOB p.Phe1455=

Q: How common is APOB p.Phe1455= (c.4365C>T) in the general population?

APOB p.Phe1455= (c.4365C>T) is common (popmax 6.77%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4365C>T · rs12720847 · VCV334144

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 6.77%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

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 -1.8	GERP -3.1
Overall
CADD	4.199	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.77% African / African-American · 5,077/75,004 alleles

Filtering AF 6.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.55%

Overall 0.369% 5,952/1,614,100 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.77%	15
Middle Eastern	0.61%	164
Remaining individualsnot grpmax-eligible	0.542%	184
Admixed American	0.488%	205
South Asian	0.0176%	5,692
European (non-Finnish)	0.0154%	6,484
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
East Asian	0.00891%	11,221

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.Phe1455=
Coding: c.4365C>T
MANE Select: NM_000384
dbSNP: rs12720847
Type: single nucleotide variant
Location: chr2:21012503 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypercholesterolemia hypercholesterolemia, familial, 1 hypercholesterolemia, autosomal dominant, type B familial hypobetalipoproteinemia 1

Similar variants

APOB p.Phe1455Leu 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
APOB p.Arg2513Ter 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-phe1455 (accessed [today's date]).

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