Is APOB p.Phe705Ile (c.2113T>A) pathogenic?

APOB p.Phe705Ile (c.2113T>A) is classified Uncertain significance in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely pathogenic (0.6091); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Phe705Ile (c.2113T>A)?

APOB p.Phe705Ile (c.2113T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is APOB p.Phe705Ile (c.2113T>A) in the general population?

APOB p.Phe705Ile (c.2113T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APOB p.Phe705Ile (c.2113T>A)?

AlphaMissense predicts likely pathogenic (score 0.6091) — an in-silico prediction, not a clinical call.

APOB p.Phe705Ile

c.2113T>A · rs375826747 · VCV3231384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6091 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.6091	likely pathogenic · top 7% in APOB
REVEL	0.521	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.91 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APOB
Protein: p.Phe705Ile
Coding: c.2113T>A
MANE Select: NM_000384
dbSNP: rs375826747
Type: single nucleotide variant
Location: chr2:21026919 (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

Similar variants

APOB p.Phe705Leu Conflicting classifications of pathogenicity ★ same residue
APOB p.Phe705= Likely benign ★ same residue
APOB p.Arg490Trp Pathogenic/Likely pathogenic ★★ same condition
APOB p.Phe705fs Pathogenic ★★ same residue
APOB c.1124+3A>G Uncertain significance ★★ same condition
APOB c.11788+4A>G Uncertain significance ★★ same condition
APOB c.12087+2T>C Uncertain significance ★★ same condition
APOB p.Ala1320Thr 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-phe705ile (accessed [today's date]).

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