Is ABL1 p.Arg89Trp (c.265C>T) pathogenic?

ABL1 p.Arg89Trp (c.265C>T) is classified Uncertain significance in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely pathogenic (0.8887); Very rare (popmax 0.00398%, nfe).

How common is ABL1 p.Arg89Trp (c.265C>T) in the general population?

ABL1 p.Arg89Trp (c.265C>T) is very rare (popmax 0.00398%, nfe) (gnomAD).

What do computational predictors say about ABL1 p.Arg89Trp (c.265C>T)?

AlphaMissense predicts likely pathogenic (score 0.8887) — an in-silico prediction, not a clinical call.

ABL1 p.Arg89Trp

c.265C>T · rs375582718 · VCV2894127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8887 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00398%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8887	likely pathogenic
REVEL	0.525	indeterminate
SaProt	LLR -10.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 903 bp · p 1.4e-15 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00398% European (non-Finnish) · 47/1,179,430 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.0031% 50/1,613,280 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00398%	25,094
Remaining individualsnot grpmax-eligible	0.0032%	31,222
South Asian	0.0011%	91,058

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.Arg89Trp
Coding: c.265C>T
MANE Select: NM_005157
dbSNP: rs375582718
Type: single nucleotide variant
Location: chr9:130854812 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 89: the sh3 domain; a β-strand

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

Similar variants

ABL1 p.Arg89= Benign ★ same residue
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

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-arg89trp (accessed [today's date]).

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