Is APOB p.Ala3707Val (c.11120C>T) pathogenic?

APOB p.Ala3707Val (c.11120C>T) is classified Benign in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). AlphaMissense: likely benign (0.2084); Ultra-rare (popmax 0.0423%, eas); Associated with hypercholesterolemia, autosomal dominant, type B.

How common is APOB p.Ala3707Val (c.11120C>T) in the general population?

APOB p.Ala3707Val (c.11120C>T) is ultra-rare (popmax 0.0423%, eas) (gnomAD).

What do computational predictors say about APOB p.Ala3707Val (c.11120C>T)?

AlphaMissense predicts likely benign (score 0.2084) — an in-silico prediction, not a clinical call.

APOB p.Ala3707Val

Q: What condition is associated with APOB p.Ala3707Val (c.11120C>T)?

APOB p.Ala3707Val (c.11120C>T) is associated with hypercholesterolemia, autosomal dominant, type B, familial hypobetalipoproteinemia 1 (ClinVar).

c.11120C>T · rs756381590 · VCV2925110

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2084 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0423%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

hypercholesterolemia, autosomal dominant, type B

Computational evidence

Protein change
AlphaMissense	0.2084	likely benign
REVEL	0.14	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.6, phastCons 0.98
Regional constraint	o/e 1.03	unconstrained · MANE · 9,629 bp · p 0.051 · regional, not allelic
Overall
CADD	18.99	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0423% East Asian · 19/44,876 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.0013% 21/1,613,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0423%	2,362
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)	8.47e-05%	1,179,944

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.Ala3707Val
Coding: c.11120C>T
MANE Select: NM_000384
dbSNP: rs756381590
Type: single nucleotide variant
Location: chr2:21005748 (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

hypercholesterolemia, autosomal dominant, type B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypobetalipoproteinemia 1

Similar variants

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
APOB p.Arg2520Ter Pathogenic/Likely 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-ala3707val (accessed [today's date]).

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