Is ABCA1 p.Ile239Val (c.715A>G) pathogenic?

ABCA1 p.Ile239Val (c.715A>G) is classified Uncertain significance in ABCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely benign (0.0823); Very rare (popmax 0.00167%, amr); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Ile239Val (c.715A>G)?

ABCA1 p.Ile239Val (c.715A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Ile239Val (c.715A>G) in the general population?

ABCA1 p.Ile239Val (c.715A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ABCA1 p.Ile239Val (c.715A>G)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

ABCA1 p.Ile239Val

c.715A>G · VCV3937905

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -5.96	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 -4.6	GERP -5.8
Regional constraint	o/e 0.95	unconstrained · MANE · 81 kb · p 0.081 · regional, not allelic
Overall
CADD	0.126	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,026 alleles

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

Overall 0.000342% 5/1,461,462 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,026
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	0.000254%	393,345

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: ABCA1
Protein: p.Ile239Val
Coding: c.715A>G
MANE Select: NM_005502
Type: single nucleotide variant
Location: chr9:104858527 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 239: an α-helix; a disulfide bond

Full ABCA1 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

Similar variants

ABCA1 c.4175+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCA1 p.Thr940Met Pathogenic/Likely pathogenic ★★ same condition
ABCA1 c.3787+5C>A Uncertain significance ★★ same condition
ABCA1 p.Ala1855Ser Uncertain significance ★★ ⚠ same condition
ABCA1 p.Ala766Ser Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1283Cys Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1342Trp Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1417Cys 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/abca1-p-ile239val (accessed [today's date]).

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