Is ABCA1 p.Ser63Pro (c.187T>C) pathogenic?

ABCA1 p.Ser63Pro (c.187T>C) is classified Uncertain significance in ABCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-14). AlphaMissense: likely pathogenic (0.9845); Absent from gnomAD v4.1; Associated with Tangier disease.

What condition is associated with ABCA1 p.Ser63Pro (c.187T>C)?

ABCA1 p.Ser63Pro (c.187T>C) is associated with Tangier disease (ClinVar).

How common is ABCA1 p.Ser63Pro (c.187T>C) in the general population?

ABCA1 p.Ser63Pro (c.187T>C) is absent from gnomAD v4.1 (gnomAD).

How is Tangier disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCA1 p.Ser63Pro (c.187T>C)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

ABCA1 p.Ser63Pro

c.187T>C · VCV4813623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Tangier disease

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic · top 10% in ABCA1
REVEL	0.935	strongly pathogenic-leaning
SaProt	LLR -10.19	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 81 kb · p 0.081 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCA1
Protein: p.Ser63Pro
Coding: c.187T>C
MANE Select: NM_005502
Type: single nucleotide variant
Location: chr9:104884542 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 63: an α-helix

Full ABCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Tangier disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal

Similar variants

ABCA1 p.Arg2080Trp Likely pathogenic ★★ same condition
ABCA1 p.Arg587Trp Pathogenic/Likely pathogenic ★★ same condition
ABCA1 p.Asn1800His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCA1 c.*2330A>T Uncertain significance ★★ same condition
ABCA1 c.*379C>T Uncertain significance ★★ same condition
ABCA1 p.Arg126Cys Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1342Trp Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg999Cys 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-ser63pro (accessed [today's date]).

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