Is ABL1 p.Pro58Ser (c.172C>T) pathogenic?

ABL1 p.Pro58Ser (c.172C>T) is classified Uncertain significance in ABL1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-28). AlphaMissense: likely benign (0.1468); Very rare (popmax 0.00891%, eas); Associated with ABL1-related disorder.

What condition is associated with ABL1 p.Pro58Ser (c.172C>T)?

ABL1 p.Pro58Ser (c.172C>T) is associated with ABL1-related disorder (ClinVar).

How common is ABL1 p.Pro58Ser (c.172C>T) in the general population?

ABL1 p.Pro58Ser (c.172C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about ABL1 p.Pro58Ser (c.172C>T)?

AlphaMissense predicts likely benign (score 0.1468) — an in-silico prediction, not a clinical call.

ABL1 p.Pro58Ser

c.172C>T · VCV3344188

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1468 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABL1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1468	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -5.08	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 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 19 kb · p 0.078 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,892 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000274% 4/1,461,878 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.Pro58Ser
Coding: c.172C>T
MANE Select: NM_005157
Type: single nucleotide variant
Location: chr9:130854156 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 58: the 'cap' region

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

Disease context

ABL1-related disorder

Similar variants

ABL1 p.Ala1001Val Uncertain significance ★★ ⚠ same condition
ABL1 p.Val938Ile Uncertain significance ★★ ⚠ same condition
ABL1 p.Ala1023Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
ABL1 p.Glu675Asp Uncertain significance ★ ⚠ same condition
ABL1 p.Glu872Lys Uncertain significance ★ ⚠ same condition
ABL1 p.Gly517Glu Uncertain significance ★ ⚠ same condition
ABL1 p.Leu740Phe Uncertain significance ★ ⚠ same condition
ABL1 p.Lys294Asn Uncertain significance ★ ⚠ 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-pro58ser (accessed [today's date]).

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