Is APOA1 p.Val54= (c.162G>C) pathogenic?

APOA1 p.Val54= (c.162G>C) is classified Benign/Likely benign in APOA1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-01). Ultra-rare (popmax 0.0725%, sas); Associated with hypoalphalipoproteinemia, primary, 2, intermediate.

What condition is associated with APOA1 p.Val54= (c.162G>C)?

APOA1 p.Val54= (c.162G>C) is associated with hypoalphalipoproteinemia, primary, 2, intermediate, familial visceral amyloidosis, hypoalphalipoproteinemia, primary, 2 (ClinVar).

How common is APOA1 p.Val54= (c.162G>C) in the general population?

APOA1 p.Val54= (c.162G>C) is ultra-rare (popmax 0.0725%, sas) (gnomAD).

APOA1 p.Val54=

c.162G>C · rs193922099 · VCV35692

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0725%, sas)

Conditions

hypoalphalipoproteinemia, primary, 2, intermediate

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 0.098	GERP 3.2
Overall
CADD	7.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0725% South Asian · 66/91,088 alleles

Filtering AF 0.0584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0533%

Overall 0.00415% 67/1,614,078 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0725%	1,380
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Val54=
Coding: c.162G>C
MANE Select: NM_000039
dbSNP: rs193922099
Type: single nucleotide variant
Location: chr11:116837039 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.66 · 31 PDB
Residue 54: a UniProt-annotated variant site (in fha2; no protein expression); an α-helix

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

Disease context

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

Also linked: familial visceral amyloidosis hypoalphalipoproteinemia, primary, 2

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-val54 (accessed [today's date]).

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