Is APOB p.Thr3164= (c.9492G>A) pathogenic?

APOB p.Thr3164= (c.9492G>A) is classified Benign/Likely benign in APOB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-15). Ultra-rare (popmax 0.0825%, mid); Associated with familial hypobetalipoproteinemia 1.

What condition is associated with APOB p.Thr3164= (c.9492G>A)?

APOB p.Thr3164= (c.9492G>A) is associated with familial hypobetalipoproteinemia 1, familial hypercholesterolemia, hypercholesterolemia, autosomal dominant, type B (ClinVar).

How common is APOB p.Thr3164= (c.9492G>A) in the general population?

APOB p.Thr3164= (c.9492G>A) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

APOB p.Thr3164=

c.9492G>A · rs200109262 · VCV695457

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Conditions

familial hypobetalipoproteinemia 1

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 0.19	GERP -2.4, phastCons 0.99
Overall
CADD	5.667	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.0114% 184/1,613,904 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.189%	529
Middle Easterngrpmax	0.0825%	1,212
Admixed American	0.0317%	3,157
Remaining individualsnot grpmax-eligible	0.0144%	6,945
South Asian	0.00439%	22,763
European (non-Finnish)	0.0022%	45,382

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr3164=
Coding: c.9492G>A
MANE Select: NM_000384
dbSNP: rs200109262
Type: single nucleotide variant
Location: chr2:21007376 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 3164: the 'heparin-binding' region

Full APOB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial hypobetalipoproteinemia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

APOB p.Thr3164Met Conflicting classifications of pathogenicity ★ same residue
APOB p.Thr3164Ser 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

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-thr3164 (accessed [today's date]).

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