Is ABCA7 p.Arg976= (c.2928C>T) pathogenic?

ABCA7 p.Arg976= (c.2928C>T) is classified Likely benign in ABCA7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-01). Ultra-rare (popmax 0.092%, afr); Associated with ABCA7-related disorder.

What condition is associated with ABCA7 p.Arg976= (c.2928C>T)?

ABCA7 p.Arg976= (c.2928C>T) is associated with ABCA7-related disorder (ClinVar).

How common is ABCA7 p.Arg976= (c.2928C>T) in the general population?

ABCA7 p.Arg976= (c.2928C>T) is ultra-rare (popmax 0.092%, afr) (gnomAD).

ABCA7 p.Arg976=

c.2928C>T · rs112434834 · VCV3037619

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.092%, afr)

Conditions

ABCA7-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -3.7
Overall
CADD	2.974	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.092% African / African-American · 69/75,040 alleles

Filtering AF 0.0745% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0682%

Overall 0.0103% 166/1,612,552 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.092%	1,088
Admixed American	0.02%	4,999
Middle Eastern	0.0166%	6,014
Remaining individualsnot grpmax-eligible	0.016%	6,247
European (non-Finnish)	0.00585%	17,099
South Asian	0.00549%	18,215

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: ABCA7
Protein: p.Arg976=
Coding: c.2928C>T
MANE Select: NM_019112
dbSNP: rs112434834
Type: single nucleotide variant
Location: chr19:1051552 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 976: an α-helix; the abc transporter 1 domain

Full ABCA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ABCA7-related disorder

Similar variants

ABCA7 c.4417-1G>C Likely pathogenic ★ same condition
ABCA7 p.Gln1083Ter Pathogenic ★ same condition
ABCA7 p.Arg1754Ter Likely pathogenic same condition
ABCA7 p.Glu269Ter Likely pathogenic same condition
ABCA7 c.790+10T>G Benign same condition
ABCA7 c.-9A>G Benign same condition
ABCA7 p.Ala1441= Likely benign same condition
ABCA7 p.Ala1864= Benign 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/abca7-p-arg976 (accessed [today's date]).

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