Is ABCA1 p.Arg2144Ter (c.6430C>T) pathogenic?

ABCA1 p.Arg2144Ter (c.6430C>T) is classified Pathogenic in ABCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). Very rare (popmax 0.00133%, afr).

How common is ABCA1 p.Arg2144Ter (c.6430C>T) in the general population?

ABCA1 p.Arg2144Ter (c.6430C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

ABCA1 p.Arg2144Ter

c.6430C>T · rs776238691 · VCV4709684

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 49 of 50
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 1.2, phastCons 1
Overall
CADD	45.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,018 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,016 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,018
European (non-Finnish)	0.000339%	294,996

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.Arg2144Ter
Coding: c.6430C>T
MANE Select: NM_005502
dbSNP: rs776238691
Type: single nucleotide variant
Location: chr9:104785611 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 2144: the abc transporter 2 domain; a β-strand

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

Similar variants

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
ABCA1 p.Asn1800His Pathogenic/Likely pathogenic ★★ ⚠ same type
ABCA1 p.Thr940Met 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-arg2144ter (accessed [today's date]).

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