Is APOA1 p.Ala39Val (c.116C>T) pathogenic?

APOA1 p.Ala39Val (c.116C>T) is classified Conflicting classifications of pathogenicity in APOA1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-18). AlphaMissense: likely benign (0.1625); Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

What condition is associated with APOA1 p.Ala39Val (c.116C>T)?

APOA1 p.Ala39Val (c.116C>T) is associated with Cardiovascular phenotype, familial visceral amyloidosis, hypoalphalipoproteinemia, primary, 1 (ClinVar).

How common is APOA1 p.Ala39Val (c.116C>T) in the general population?

APOA1 p.Ala39Val (c.116C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about APOA1 p.Ala39Val (c.116C>T)?

AlphaMissense predicts likely benign (score 0.1625) — an in-silico prediction, not a clinical call.

APOA1 p.Ala39Val

c.116C>T · rs746314593 · VCV302509

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1625 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1625	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR 0.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1.4
Regional constraint	o/e 1.01	unconstrained · MANE · 1,576 bp · p 0.87 · regional, not allelic
Overall
CADD	6.299	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 0.00133% African / African-American · 1/74,924 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,986 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,924
European (non-Finnish)	0.000254%	393,343

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.Ala39Val
Coding: c.116C>T
MANE Select: NM_000039
dbSNP: rs746314593
Type: single nucleotide variant
Location: chr11:116837085 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.66 · 31 PDB
Residue 39: 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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial visceral amyloidosis hypoalphalipoproteinemia, primary, 1

Similar variants

APOA1 p.Gly50Arg Pathogenic ★★ same condition
APOA1 p.Ala176Thr Uncertain significance ★★ ⚠ same condition
APOA1 p.Ala176Val Uncertain significance ★★ ⚠ same condition
APOA1 p.Ala204Val Uncertain significance ★★ ⚠ same condition
APOA1 p.Ala218Thr Uncertain significance ★★ ⚠ same condition
APOA1 p.Ala256Thr Uncertain significance ★★ ⚠ same condition
APOA1 p.Arg140Leu Uncertain significance ★★ ⚠ same condition
APOA1 p.Arg175Gly 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-ala39val (accessed [today's date]).

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