Is ABL1 p.Glu675Asp (c.2025G>C) pathogenic?

ABL1 p.Glu675Asp (c.2025G>C) is classified Uncertain significance in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-03). AlphaMissense: likely benign (0.0609); Very rare (popmax 0.000339%, nfe); Associated with ABL1-related disorder.

What condition is associated with ABL1 p.Glu675Asp (c.2025G>C)?

ABL1 p.Glu675Asp (c.2025G>C) is associated with ABL1-related disorder (ClinVar).

How common is ABL1 p.Glu675Asp (c.2025G>C) in the general population?

ABL1 p.Glu675Asp (c.2025G>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about ABL1 p.Glu675Asp (c.2025G>C)?

AlphaMissense predicts likely benign (score 0.0609) — an in-silico prediction, not a clinical call.

ABL1 p.Glu675Asp

c.2025G>C · rs1831524231 · VCV2636140

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0609 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABL1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0609	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -6.19	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 2	GERP -0.83, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,156 bp · p 0.054 · regional, not allelic
Overall
CADD	13.91	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 0.000339% European (non-Finnish) · 4/1,179,308 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,459,402 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.Glu675Asp
Coding: c.2025G>C
MANE Select: NM_005157
dbSNP: rs1831524231
Type: single nucleotide variant
Location: chr9:130884315 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 675: the 'disordered' region

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

Disease context

ABL1-related disorder

Similar variants

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ABL1 p.Val938Ile Uncertain significance ★★ ⚠ same condition
ABL1 p.Ala1023Thr Conflicting classifications of pathogenicity ★ ⚠ 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
ABL1 p.Thr117Met Conflicting classifications of pathogenicity ★ ⚠ 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-glu675asp (accessed [today's date]).

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