Is APOB p.Val1104= (c.3312C>T) pathogenic?

APOB p.Val1104= (c.3312C>T) is classified Likely benign in APOB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-22). Ultra-rare (popmax 0.0166%, mid); Associated with familial hypercholesterolemia.

What condition is associated with APOB p.Val1104= (c.3312C>T)?

APOB p.Val1104= (c.3312C>T) is associated with familial hypercholesterolemia, hypercholesterolemia, autosomal dominant, type B, familial hypobetalipoproteinemia 1 (ClinVar).

How common is APOB p.Val1104= (c.3312C>T) in the general population?

APOB p.Val1104= (c.3312C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

APOB p.Val1104=

c.3312C>T · rs780454824 · VCV630324

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

familial hypercholesterolemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.14	GERP -1.6, phastCons 0.001
Overall
CADD	7.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,030 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000262%

Overall 0.00106% 17/1,604,884 alleles · ultra-rare exomes 13/1,452,760 · genomes 4/152,124 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,030
Admixed American	0.00333%	29,995
East Asian	0.00223%	44,828
South Asian	0.0022%	45,448
Remaining individualsnot grpmax-eligible	0.00161%	62,162
African / African-American	0.00134%	74,732
European (non-Finnish)	0.000768%	130,195

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.Val1104=
Coding: c.3312C>T
MANE Select: NM_000384
dbSNP: rs780454824
Type: single nucleotide variant
Location: chr2:21016459 (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

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

Similar variants

APOB p.Val1104Ile 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-val1104 (accessed [today's date]).

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