Is ABCA1 p.Arg83His (c.248G>A) pathogenic?

ABCA1 p.Arg83His (c.248G>A) is classified Conflicting classifications of pathogenicity in ABCA1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-08). AlphaMissense: likely benign (0.1414); Very rare (popmax 0.00551%, nfe).

How common is ABCA1 p.Arg83His (c.248G>A) in the general population?

ABCA1 p.Arg83His (c.248G>A) is very rare (popmax 0.00551%, nfe) (gnomAD).

What do computational predictors say about ABCA1 p.Arg83His (c.248G>A)?

AlphaMissense predicts likely benign (score 0.1414) — an in-silico prediction, not a clinical call.

ABCA1 p.Arg83His

c.248G>A · VCV3373617

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1414 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00551%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1414	likely benign
REVEL	0.726	pathogenic-leaning
SaProt	LLR -5.66	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 81 kb · p 0.081 · regional, not allelic
Overall
CADD	27.2	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 0.00551% European (non-Finnish) · 65/1,180,036 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00403%

Overall 0.00452% 73/1,614,080 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00551%	18,154
African / African-American	0.004%	24,977
South Asian	0.00329%	30,360
Remaining individualsnot grpmax-eligible	0.0032%	31,245

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.Arg83His
Coding: c.248G>A
MANE Select: NM_005502
Type: single nucleotide variant
Location: chr9:104884481 (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

Similar variants

ABCA1 p.Arg83Cys Uncertain significance ★ ⚠ same residue
ABCA1 p.Arg83Ser Uncertain significance ★ ⚠ same residue
ABCA1 c.4175+1G>T Pathogenic/Likely pathogenic ★★ same type
ABCA1 c.4274+1G>A Likely pathogenic ★★ same type
ABCA1 c.5237+3A>C Likely pathogenic ★★ same type
ABCA1 p.Arg2080Trp Likely pathogenic ★★ same type
ABCA1 p.Arg557Ter Pathogenic/Likely pathogenic ★★ same type
ABCA1 p.Arg587Trp Pathogenic/Likely pathogenic ★★ same type

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-arg83his (accessed [today's date]).

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