Is ABCA1 p.Pro85= (c.255G>A) pathogenic?

ABCA1 p.Pro85= (c.255G>A) is classified Likely benign in ABCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-29). Very rare (popmax 0.00329%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Pro85= (c.255G>A)?

ABCA1 p.Pro85= (c.255G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Pro85= (c.255G>A) in the general population?

ABCA1 p.Pro85= (c.255G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

ABCA1 p.Pro85=

c.255G>A · VCV3832585

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

Cardiovascular phenotype

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 -5	GERP -5.2
Overall
CADD	8.017	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,086 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.0015% 22/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,362
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.00153%	65,556

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.Pro85=
Coding: c.255G>A
MANE Select: NM_005502
Type: single nucleotide variant
Location: chr9:104884474 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 85: a disulfide bond; a UniProt-annotated variant site (in fha1; alabama)

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 p.Pro85Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA1 p.Pro85Ser Uncertain significance ★ ⚠ same residue
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

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-pro85 (accessed [today's date]).

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