Is ABCA7 p.Arg93fs (c.273del) pathogenic?

ABCA7 p.Arg93fs (c.273del) is classified Likely pathogenic in ABCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-24). Very rare (popmax 0.00341%, nfe).

How common is ABCA7 p.Arg93fs (c.273del) in the general population?

ABCA7 p.Arg93fs (c.273del) is very rare (popmax 0.00341%, nfe) (gnomAD).

ABCA7 p.Arg93fs

c.273del · rs777874744 · VCV1678180

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00341%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 47
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP -3.4, phastCons 1
Overall
CADD	22.6	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 0.00341% European (non-Finnish) · 40/1,174,270 alleles

Filtering AF 0.00257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00226%

Overall 0.00251% 40/1,590,604 alleles · very rare

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.Arg93fs
Coding: c.273del
MANE Select: NM_019112
dbSNP: rs777874744
Type: Deletion
Location: chr19:1041941 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 93: a disulfide bond

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

Similar variants

ABCA7 p.Glu572fs Likely pathogenic ★ same type
ABCA7 p.Thr849fs Pathogenic ★ same type
ABCA7 p.Glu2046fs Uncertain significance ★ same type
ABCA7 p.Leu1403fs Conflicting classifications of pathogenicity ★ same type
ABCA7 p.Leu396fs Conflicting classifications of pathogenicity ★ same type
ABCA7 p.Pro1205fs Uncertain significance ★ same type
ABCA7 p.Pro1367fs Uncertain significance ★ same type
ABCA7 p.Ser958fs Uncertain significance ★ 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/abca7-p-arg93fs (accessed [today's date]).

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