Is APOA1 p.Ala3= (c.9T>C) pathogenic?

APOA1 p.Ala3= (c.9T>C) is classified Benign/Likely benign in APOA1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-10-01). Ultra-rare (popmax 0.0813%, sas); Associated with hypoalphalipoproteinemia, primary, 2.

What condition is associated with APOA1 p.Ala3= (c.9T>C)?

APOA1 p.Ala3= (c.9T>C) is associated with hypoalphalipoproteinemia, primary, 2, familial visceral amyloidosis, hypoalphalipoproteinemia, primary, 1 (ClinVar).

How common is APOA1 p.Ala3= (c.9T>C) in the general population?

APOA1 p.Ala3= (c.9T>C) is ultra-rare (popmax 0.0813%, sas) (gnomAD).

How is Apolipoprotein A-I deficiency inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

APOA1 p.Ala3=

c.9T>C · rs141383703 · VCV302511

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0813%, sas)

Conditions

hypoalphalipoproteinemia, primary, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.119	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -4.5
Overall
CADD	1.265	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0813% South Asian · 69/84,920 alleles

Filtering AF 0.0658% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0602%

Overall 0.021% 327/1,560,830 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0813%	1,231
Middle Eastern	0.0333%	3,001
Remaining individualsnot grpmax-eligible	0.0215%	4,653
European (non-Finnish)	0.0202%	4,944
Admixed American	0.0135%	7,385
African / African-American	0.00406%	24,622

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: APOA1
Protein: p.Ala3=
Coding: c.9T>C
MANE Select: NM_000039
dbSNP: rs141383703
Type: single nucleotide variant
Location: chr11:116837379 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.66 · 31 PDB

Full APOA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypoalphalipoproteinemia, primary, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial visceral amyloidosis hypoalphalipoproteinemia, primary, 1 hypoalphalipoproteinemia, primary, 2, intermediate

For Apolipoprotein A-I deficiency (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

APOA1 p.Gln23Ter Pathogenic ★★ same condition
APOA1 p.Gly50Arg Pathogenic ★★ same condition
APOA1 c.-21+22G>A Uncertain significance ★★ same condition
APOA1 p.Ala220Pro Uncertain significance ★★ ⚠ same condition
APOA1 p.Arg34Leu Uncertain significance ★★ same condition
APOA1 p.Asp127Asn Uncertain significance ★★ ⚠ same condition
APOA1 p.Glu160Asp Uncertain significance ★★ ⚠ same condition
APOA1 p.Glu170Lys 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/apoa1-p-ala3 (accessed [today's date]).

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