Is ABL1 p.Leu1012fs (c.3034_3035del) pathogenic?

ABL1 p.Leu1012fs (c.30343035del) is classified Uncertain significance in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-14). Very rare (popmax 0.00167%, amr).

How common is ABL1 p.Leu1012fs (c.3034_3035del) in the general population?

ABL1 p.Leu1012fs (c.3034_3035del) is very rare (popmax 0.00167%, amr) (gnomAD).

ABL1 p.Leu1012fs

c.3034_3035del · VCV4728766

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,032 alleles

Overall 6.84e-05% 1/1,461,314 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: ABL1
Protein: p.Leu1012fs
Coding: c.3034_3035del
MANE Select: NM_005157
Type: Microsatellite
Location: chr9:130885321 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 1012: the 'f-actin-binding' region

Full ABL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABL1 p.Leu1012= Likely benign ★ same residue
ABL1 p.Glu704del Uncertain significance ★ same type
ABL1 p.Lys609_Thr610insLys Uncertain significance ★ same type
ABL1 p.Lys609del Conflicting classifications of pathogenicity ★ same type
ABL1 p.Lys689del Uncertain significance ★ same type
ABL1 c.908-7_908-5del Likely benign ★ 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/abl1-p-leu1012fs (accessed [today's date]).

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