Is ABL1 p.Pro63Leu (c.188C>T) pathogenic?

ABL1 p.Pro63Leu (c.188C>T) is classified Uncertain significance in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-07). AlphaMissense: likely pathogenic (0.8496); Absent from gnomAD v4.1.

How common is ABL1 p.Pro63Leu (c.188C>T) in the general population?

ABL1 p.Pro63Leu (c.188C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABL1 p.Pro63Leu (c.188C>T)?

AlphaMissense predicts likely pathogenic (score 0.8496) — an in-silico prediction, not a clinical call.

ABL1 p.Pro63Leu

c.188C>T · rs2132956429 · VCV1704865

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8496 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8496	likely pathogenic
REVEL	0.435	indeterminate
SaProt	LLR -9.89	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 19 kb · p 0.078 · regional, not allelic
Overall
CADD	29.9	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.Pro63Leu
Coding: c.188C>T
MANE Select: NM_005157
dbSNP: rs2132956429
Type: single nucleotide variant
Location: chr9:130854172 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 63: the sh3 domain; an α-helix

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

Similar variants

ABL1 p.Ala337Thr Pathogenic ★★ ⚠ same type
ABL1 p.Ala433Thr Likely pathogenic ★★ ⚠ same type
ABL1 p.Asp504Gly Likely pathogenic ★★ ⚠ same type
ABL1 p.Glu509Lys Pathogenic/Likely pathogenic ★★ same type
ABL1 p.Gly254Arg Pathogenic/Likely pathogenic ★★ same type
ABL1 p.Pro230Leu Likely pathogenic ★★ ⚠ same type
ABL1 p.Trp99Arg Likely pathogenic ★★ same type
ABL1 p.Tyr226Cys Pathogenic/Likely pathogenic ★★ ⚠ same type

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-pro63leu (accessed [today's date]).

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