Is ABL1 p.Trp48Ser (c.143G>C) pathogenic?

ABL1 p.Trp48Ser (c.143G>C) is classified Likely pathogenic in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely pathogenic (0.9978); Absent from gnomAD v4.1; Associated with congenital heart defects and skeletal malformations syndrome.

What condition is associated with ABL1 p.Trp48Ser (c.143G>C)?

ABL1 p.Trp48Ser (c.143G>C) is associated with congenital heart defects and skeletal malformations syndrome (ClinVar).

How common is ABL1 p.Trp48Ser (c.143G>C) in the general population?

ABL1 p.Trp48Ser (c.143G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABL1 p.Trp48Ser (c.143G>C)?

AlphaMissense predicts likely pathogenic (score 0.9978) — an in-silico prediction, not a clinical call.

ABL1 p.Trp48Ser

c.143G>C · rs2132956266 · VCV1699204

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital heart defects and skeletal malformations syndrome

Computational evidence

Protein change
AlphaMissense	0.9978	likely pathogenic ✓ concordant with ClinVar · top 10% in ABL1
REVEL	0.578	indeterminate
SaProt	LLR -3.82	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 19 kb · p 0.078 · regional, not allelic
Overall
CADD	33.0	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.

Variant & gene context

Gene: ABL1
Protein: p.Trp48Ser
Coding: c.143G>C
MANE Select: NM_005157
dbSNP: rs2132956266
Type: single nucleotide variant
Location: chr9:130854127 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 48: the 'cap' 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.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-trp48ser (accessed [today's date]).

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