Is ABL1 p.Glu623= (c.1869G>A) pathogenic?

ABL1 p.Glu623= (c.1869G>A) is classified Benign in ABL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-04). Common (popmax 5.22%, afr) — too common for a highly-penetrant pathogenic allele.

ABL1 p.Glu623=

Q: How common is ABL1 p.Glu623= (c.1869G>A) in the general population?

ABL1 p.Glu623= (c.1869G>A) is common (popmax 5.22%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1869G>A · rs34717358 · VCV1601121

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.22%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -1.9, phastCons 1
Overall
CADD	6.076	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.22% African / African-American · 3,919/75,018 alleles

Filtering AF 5.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.03%

Overall 1.74% 28,134/1,613,112 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	14.5%	7
African / African-Americangrpmax	5.22%	19
Middle Eastern	5.01%	20
Ashkenazi Jewishnot grpmax-eligible	4.88%	20
Finnishnot grpmax-eligible	3.82%	26
Remaining individualsnot grpmax-eligible	2.43%	41
Admixed American	2.42%	41
European (non-Finnish)	1.43%	70
South Asian	0.114%	875
East Asian	0.00223%	44,888

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu623=
Coding: c.1869G>A
MANE Select: NM_005157
dbSNP: rs34717358
Type: single nucleotide variant
Location: chr9:130884159 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 623: the 'disordered' region

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-glu623 (accessed [today's date]).

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