Is ABCA1 p.Arg83Cys (c.247C>T) pathogenic?

ABCA1 p.Arg83Cys (c.247C>T) is classified Uncertain significance in ABCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: ambiguous (0.4996); Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Arg83Cys (c.247C>T)?

ABCA1 p.Arg83Cys (c.247C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Arg83Cys (c.247C>T) in the general population?

ABCA1 p.Arg83Cys (c.247C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ABCA1 p.Arg83Cys (c.247C>T)?

AlphaMissense predicts ambiguous (score 0.4996) — an in-silico prediction, not a clinical call.

ABCA1 p.Arg83Cys

c.247C>T · VCV4238671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4996	ambiguous
REVEL	0.888	moderately pathogenic-leaning
SaProt	LLR -8.71	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 81 kb · p 0.081 · regional, not allelic
Overall
CADD	33.0	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 0.00223% East Asian · 1/44,894 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,614,102 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,894
European (non-Finnish)	0.000508%	196,674

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.Arg83Cys
Coding: c.247C>T
MANE Select: NM_005502
Type: single nucleotide variant
Location: chr9:104884482 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 83: 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 p.Arg83Ser Uncertain significance ★ ⚠ same residue
ABCA1 p.Arg83His Conflicting classifications of pathogenicity ★ ⚠ 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-arg83cys (accessed [today's date]).

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