Is ABL1 p.Arg819Gln (c.2456G>A) pathogenic?

ABL1 p.Arg819Gln (c.2456G>A) is classified Conflicting classifications of pathogenicity in ABL1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.0911); Very rare (popmax 0.00834%, amr); Associated with congenital heart defects and skeletal malformations syndrome.

How common is ABL1 p.Arg819Gln (c.2456G>A) in the general population?

ABL1 p.Arg819Gln (c.2456G>A) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about ABL1 p.Arg819Gln (c.2456G>A)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

ABL1 p.Arg819Gln

Q: What condition is associated with ABL1 p.Arg819Gln (c.2456G>A)?

ABL1 p.Arg819Gln (c.2456G>A) is associated with congenital heart defects and skeletal malformations syndrome, chronic myeloid leukemia (ClinVar).

c.2456G>A · VCV3596486

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital heart defects and skeletal malformations syndrome

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -7.43	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 10	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,156 bp · p 0.054 · regional, not allelic
Overall
CADD	27.7	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

Grpmax group 0.00834% Admixed American · 5/59,988 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00124% 20/1,612,306 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,998
South Asian	0.00439%	22,766
Remaining individualsnot grpmax-eligible	0.0032%	31,229
African / African-American	0.00133%	74,910
European (non-Finnish)	0.000678%	147,475

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.Arg819Gln
Coding: c.2456G>A
MANE Select: NM_005157
Type: single nucleotide variant
Location: chr9:130884746 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 819: the 'disordered' region

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.Arg819Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-arg819gln (accessed [today's date]).

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