Is ABCA1 p.Pro853Ser (c.2557C>T) pathogenic?

ABCA1 p.Pro853Ser (c.2557C>T) is classified Uncertain significance in ABCA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-07). AlphaMissense: ambiguous (0.3994); Very rare (popmax 0.0022%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Pro853Ser (c.2557C>T)?

ABCA1 p.Pro853Ser (c.2557C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Pro853Ser (c.2557C>T) in the general population?

ABCA1 p.Pro853Ser (c.2557C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ABCA1 p.Pro853Ser (c.2557C>T)?

AlphaMissense predicts ambiguous (score 0.3994) — an in-silico prediction, not a clinical call.

ABCA1 p.Pro853Ser

c.2557C>T · rs1159795276 · VCV1500815

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3994	ambiguous
REVEL	0.603	indeterminate
SaProt	LLR -8.11	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 81 kb · p 0.081 · regional, not allelic
Overall
CADD	27.6	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 0.0022% South Asian · 2/91,064 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000274% 4/1,461,506 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,532
European (non-Finnish)	0.000169%	590,005

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.Pro853Ser
Coding: c.2557C>T
MANE Select: NM_005502
dbSNP: rs1159795276
Type: single nucleotide variant
Location: chr9:104824564 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB

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.Pro853Thr 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
ABCA1 p.Arg1342Trp 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-pro853ser (accessed [today's date]).

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