Is ABL1 p.Pro784Leu (c.2351C>T) pathogenic?

ABL1 p.Pro784Leu (c.2351C>T) is classified Likely pathogenic in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-24). AlphaMissense: likely benign (0.2077); Very rare (popmax 0.00133%, afr); Associated with congenital heart defects and skeletal malformations syndrome.

What condition is associated with ABL1 p.Pro784Leu (c.2351C>T)?

ABL1 p.Pro784Leu (c.2351C>T) is associated with congenital heart defects and skeletal malformations syndrome (ClinVar).

How common is ABL1 p.Pro784Leu (c.2351C>T) in the general population?

ABL1 p.Pro784Leu (c.2351C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ABL1 p.Pro784Leu (c.2351C>T)?

AlphaMissense predicts likely benign (score 0.2077) — an in-silico prediction, not a clinical call.

ABL1 p.Pro784Leu

c.2351C>T · rs1355021408 · VCV1029154

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2077 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital heart defects and skeletal malformations syndrome

Computational evidence

Protein change
AlphaMissense	0.2077	likely benign ⚠ discordant with ClinVar
REVEL	0.201	benign-leaning
SaProt	LLR -8.14	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 7.7	GERP 0.94, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,156 bp · p 0.054 · regional, not allelic
Overall
CADD	21.5	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 0.00133% African / African-American · 1/75,040 alleles

Overall 6.84e-05% 1/1,460,988 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.Pro784Leu
Coding: c.2351C>T
MANE Select: NM_005157
dbSNP: rs1355021408
Type: single nucleotide variant
Location: chr9:130884641 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 784: 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

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

Onset: Neonatal

Similar variants

ABL1 p.Pro784Arg Uncertain significance ★★ ⚠ same residue
ABL1 p.Pro784= Benign ★★ same residue
ABL1 p.Pro784Ala 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

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-pro784leu (accessed [today's date]).

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