Is APOB p.Ile688= (c.2064C>T) pathogenic?

APOB p.Ile688= (c.2064C>T) is classified Likely benign in APOB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-28). Ultra-rare (popmax 0.0161%, afr); Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Ile688= (c.2064C>T)?

APOB p.Ile688= (c.2064C>T) is associated with Cardiovascular phenotype, familial hypercholesterolemia (ClinVar).

How common is APOB p.Ile688= (c.2064C>T) in the general population?

APOB p.Ile688= (c.2064C>T) is ultra-rare (popmax 0.0161%, afr) (gnomAD).

APOB p.Ile688=

c.2064C>T · rs774188993 · VCV923785

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0161%, afr)

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 -3	GERP -3.8
Overall
CADD	2.744	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0161% African / African-American · 12/74,752 alleles

Filtering AF 0.00923% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00723%

Overall 0.00156% 25/1,607,644 alleles · ultra-rare exomes 16/1,455,502 · genomes 9/152,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0161%	6,229
East Asian	0.00223%	44,848
Remaining individualsnot grpmax-eligible	0.0016%	62,318
Finnishnot grpmax-eligible	0.00156%	64,020
European (non-Finnish)	0.000852%	117,423

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.Ile688=
Coding: c.2064C>T
MANE Select: NM_000384
dbSNP: rs774188993
Type: single nucleotide variant
Location: chr2:21027831 (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

Similar variants

APOB p.Ile688Thr Uncertain significance ★ ⚠ same residue
APOB p.Ile688Phe Likely benign ★ 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.Arg490Trp Pathogenic/Likely pathogenic ★★ same condition
APOB c.1124+3A>G Uncertain significance ★★ same condition
APOB c.11788+4A>G 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-ile688 (accessed [today's date]).

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