Is APOB p.Phe4495= (c.13485T>C) pathogenic?

APOB p.Phe4495= (c.13485T>C) is classified Likely benign in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-03). Ultra-rare (popmax 0.0165%, mid); Associated with familial hypercholesterolemia.

What condition is associated with APOB p.Phe4495= (c.13485T>C)?

APOB p.Phe4495= (c.13485T>C) is associated with familial hypercholesterolemia (ClinVar).

How common is APOB p.Phe4495= (c.13485T>C) in the general population?

APOB p.Phe4495= (c.13485T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

APOB p.Phe4495=

c.13485T>C · VCV3393006

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

familial hypercholesterolemia

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 2.1	GERP -2.9, phastCons 0.99
Overall
CADD	6.084	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00062% 10/1,614,096 alleles · ultra-rare exomes 10/1,461,744 · genomes 0/152,352 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.00988%	10,120

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.Phe4495=
Coding: c.13485T>C
MANE Select: NM_000384
Type: single nucleotide variant
Location: chr2:21001937 (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 hypercholesterolemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APOB p.Phe4495Tyr Uncertain significance ★ ⚠ same residue
APOB p.Arg2085Ter Pathogenic/Likely pathogenic ★★ same condition
APOB p.Arg3527Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
APOB p.Arg3527Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
APOB p.Ala1695Val Uncertain significance ★★ ⚠ same condition
APOB p.Ala68Thr Uncertain significance ★★ ⚠ same condition
APOB p.Arg3183Gly Uncertain significance ★★ ⚠ same condition
APOB p.Arg3311Ile Uncertain significance ★★ ⚠ 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-phe4495 (accessed [today's date]).

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