Is ABL1 p.Phe311Leu (c.931T>C) pathogenic?

ABL1 p.Phe311Leu (c.931T>C) is classified Pathogenic in ABL1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2002-08-01). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1; Associated with chronic myeloid leukemia.

What condition is associated with ABL1 p.Phe311Leu (c.931T>C)?

ABL1 p.Phe311Leu (c.931T>C) is associated with chronic myeloid leukemia (ClinVar).

How common is ABL1 p.Phe311Leu (c.931T>C) in the general population?

ABL1 p.Phe311Leu (c.931T>C) is absent from gnomAD v4.1 (gnomAD).

How is Chronic myeloid leukemia inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABL1 p.Phe311Leu (c.931T>C)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

ABL1 p.Phe311Leu

c.931T>C · rs137853304 · VCV12628

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

chronic myeloid leukemia

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic ✓ concordant with ClinVar · top 5% in ABL1
REVEL	0.506	indeterminate
SaProt	LLR -8.54	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 10 kb · p 1.5e-16 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

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.

Cancer therapy — CIViC

Disease	Therapies	Level	Significance
Chronic Myeloid Leukemia	Bosutinib	C	Resistance
Chronic Myeloid Leukemia	Dasatinib	C	Sensitivity/Response
Chronic Myeloid Leukemia	Dasatinib	D	Sensitivity/Response
Chronic Myeloid Leukemia	Imatinib Mesylate,Nilotinib	D	Resistance

Variant & gene context

Gene: ABL1
Protein: p.Phe311Leu
Coding: c.931T>C
MANE Select: NM_005157
dbSNP: rs137853304
Type: single nucleotide variant
Location: chr9:130872883 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 311: the protein kinase domain

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

Disease context

chronic myeloid leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Chronic myeloid leukemia (Orphanet):

Inheritance: Not applicable
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ABL1 c.822+16C>G Benign/Likely benign ★★ same condition
ABL1 p.Ala633= Benign/Likely benign ★★ same condition
ABL1 p.Gly706Val Likely benign ★★ ⚠ same condition
ABL1 p.Ser679Ala Benign/Likely benign ★★ same condition
ABL1 p.Thr83= Benign/Likely benign ★★ same condition
ABL1 p.Arg819Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
ABL1 p.Glu576Gln Uncertain significance ★ ⚠ same condition
ABL1 p.Phe311fs Uncertain significance ★ same residue

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-phe311leu (accessed [today's date]).

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