Is ABL1 p.Leu740Phe (c.2220G>T) pathogenic?

ABL1 p.Leu740Phe (c.2220G>T) is classified Uncertain significance in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-19). AlphaMissense: likely benign (0.0988); Absent from gnomAD v4.1; Associated with ABL1-related disorder.

What condition is associated with ABL1 p.Leu740Phe (c.2220G>T)?

ABL1 p.Leu740Phe (c.2220G>T) is associated with ABL1-related disorder (ClinVar).

How common is ABL1 p.Leu740Phe (c.2220G>T) in the general population?

ABL1 p.Leu740Phe (c.2220G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABL1 p.Leu740Phe (c.2220G>T)?

AlphaMissense predicts likely benign (score 0.0988) — an in-silico prediction, not a clinical call.

ABL1 p.Leu740Phe

c.2220G>T · rs2133036317 · VCV2632509

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0988 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABL1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0988	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -7.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP -0.38, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,156 bp · p 0.054 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABL1
Protein: p.Leu740Phe
Coding: c.2220G>T
MANE Select: NM_005157
dbSNP: rs2133036317
Type: single nucleotide variant
Location: chr9:130884510 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 740: the 'disordered' region

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

Disease context

ABL1-related disorder

Similar variants

ABL1 p.Leu740= Likely benign ★ same residue
ABL1 p.Ala1001Val Uncertain significance ★★ ⚠ same condition
ABL1 p.Val938Ile Uncertain significance ★★ ⚠ same condition
ABL1 p.Ala1023Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
ABL1 p.Glu675Asp Uncertain significance ★ ⚠ same condition
ABL1 p.Glu872Lys Uncertain significance ★ ⚠ same condition
ABL1 p.Gly517Glu Uncertain significance ★ ⚠ same condition
ABL1 p.Lys294Asn Uncertain significance ★ ⚠ 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/abl1-p-leu740phe (accessed [today's date]).

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