Is ABL1 p.Thr83= (c.249T>G) pathogenic?

ABL1 p.Thr83= (c.249T>G) is classified Benign/Likely benign in ABL1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.78%, mid); Associated with congenital heart defects and skeletal malformations syndrome.

How common is ABL1 p.Thr83= (c.249T>G) in the general population?

ABL1 p.Thr83= (c.249T>G) is low-frequency (popmax 2.78%, mid) (gnomAD).

ABL1 p.Thr83=

Q: What condition is associated with ABL1 p.Thr83= (c.249T>G)?

ABL1 p.Thr83= (c.249T>G) is associated with congenital heart defects and skeletal malformations syndrome, chronic myeloid leukemia (ClinVar).

c.249T>G · rs111886835 · VCV719810

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.78%, mid)

Conditions

congenital heart defects and skeletal malformations syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP -1.5, phastCons 1
Overall
CADD	8.506	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.78% Middle Eastern · 168/6,054 alleles

Filtering AF 2.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.3%

Overall 0.651% 10,508/1,613,274 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	3.7%	27
Middle Easterngrpmax	2.78%	36
Remaining individualsnot grpmax-eligible	0.965%	104
European (non-Finnish)	0.638%	157
South Asian	0.578%	173
Admixed American	0.515%	194
Finnishnot grpmax-eligible	0.309%	323
African / African-American	0.111%	904
Amishnot grpmax-eligible	0.11%	912
East Asian	0.00223%	44,870

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr83=
Coding: c.249T>G
MANE Select: NM_005157
dbSNP: rs111886835
Type: single nucleotide variant
Location: chr9:130854233 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 83: the sh3 domain

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

Disease context

congenital heart defects and skeletal malformations syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: chronic myeloid leukemia

For Marfanoid habitus-facial dysmorphism-skeletal abnormality-heart defect syndrome (Orphanet):

Onset: Neonatal

Similar variants

ABL1 p.Ala337Thr Pathogenic ★★ ⚠ same condition
ABL1 p.Ala433Thr Likely pathogenic ★★ ⚠ same condition
ABL1 p.Asp504Gly Likely pathogenic ★★ ⚠ same condition
ABL1 p.Glu509Lys Pathogenic/Likely pathogenic ★★ same condition
ABL1 p.Gly254Arg Pathogenic/Likely pathogenic ★★ same condition
ABL1 p.Pro230Leu Likely pathogenic ★★ ⚠ same condition
ABL1 p.Trp99Arg Likely pathogenic ★★ same condition
ABL1 p.Tyr226Cys Pathogenic/Likely pathogenic ★★ ⚠ 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-thr83 (accessed [today's date]).

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