Is ABL1 p.Arg191Cys (c.571C>T) pathogenic?

ABL1 p.Arg191Cys (c.571C>T) is classified Conflicting classifications of pathogenicity in ABL1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-13). AlphaMissense: likely pathogenic (0.7764); Very rare (popmax 0.00415%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABL1 p.Arg191Cys (c.571C>T)?

ABL1 p.Arg191Cys (c.571C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABL1 p.Arg191Cys (c.571C>T) in the general population?

ABL1 p.Arg191Cys (c.571C>T) is very rare (popmax 0.00415%, nfe) (gnomAD).

What do computational predictors say about ABL1 p.Arg191Cys (c.571C>T)?

AlphaMissense predicts likely pathogenic (score 0.7764) — an in-silico prediction, not a clinical call.

ABL1 p.Arg191Cys

c.571C>T · VCV3436008

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7764 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7764	likely pathogenic
REVEL	0.848	moderately pathogenic-leaning
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 7,716 bp · p 0.84 · 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

Grpmax group 0.00415% European (non-Finnish) · 49/1,180,014 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.0031% 50/1,613,868 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00415%	24,082
African / African-American	0.00134%	74,864

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.Arg191Cys
Coding: c.571C>T
MANE Select: NM_005157
Type: single nucleotide variant
Location: chr9:130862784 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 191: a β-strand; the sh2 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABL1 p.Arg191Leu Uncertain significance ★ ⚠ same residue
ABL1 p.Ala767Val Uncertain significance ★★ ⚠ same condition
ABL1 p.Arg1016His Uncertain significance ★★ ⚠ same condition
ABL1 p.Arg771Gly Uncertain significance ★★ ⚠ same condition
ABL1 p.Asn1088His Uncertain significance ★★ ⚠ same condition
ABL1 p.Asn120Thr Uncertain significance ★★ ⚠ same condition
ABL1 p.Asn414Lys Uncertain significance ★★ ⚠ same condition
ABL1 p.Glu123Gln 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-arg191cys (accessed [today's date]).

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