Is ABCA12 p.Arg945fs (c.2833dup) pathogenic?

ABCA12 p.Arg945fs (c.2833dup) is classified Pathogenic in ABCA12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-20). Very rare (popmax 8.48e-05%, nfe).

How common is ABCA12 p.Arg945fs (c.2833dup) in the general population?

ABCA12 p.Arg945fs (c.2833dup) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ABCA12 p.Arg945fs

c.2833dup · rs1700146530 · VCV932573

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, 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 21 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.1	GERP 0.48, phastCons 0.056

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,764 alleles

Overall 6.84e-05% 1/1,461,468 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: ABCA12
Protein: p.Arg945fs
Coding: c.2833dup
MANE Select: NM_173076
dbSNP: rs1700146530
Type: Duplication
Location: chr2:215001587 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 945: a UniProt-annotated variant site (in arci4b)

Full ABCA12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA12 p.Leu640fs Likely pathogenic ★★ same type
ABCA12 p.Leu758fs Pathogenic/Likely pathogenic ★★ same type
ABCA12 c.7240-23_7240-20dup Benign/Likely benign ★★ same type
ABCA12 p.Arg672fs Pathogenic ★ same type
ABCA12 p.Arg830fs Likely pathogenic ★ same type
ABCA12 p.Asn1671fs Pathogenic ★ same type
ABCA12 p.Asp1720fs Pathogenic ★ same type
ABCA12 p.Lys1304fs 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/abca12-p-arg945fs (accessed [today's date]).

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