Is ABL1 p.Pro869Ser (c.2605C>T) pathogenic?

ABL1 p.Pro869Ser (c.2605C>T) is classified Benign in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-16). AlphaMissense: likely benign (0.0634); Very rare (popmax 0.00221%, sas).

How common is ABL1 p.Pro869Ser (c.2605C>T) in the general population?

ABL1 p.Pro869Ser (c.2605C>T) is very rare (popmax 0.00221%, sas) (gnomAD).

What do computational predictors say about ABL1 p.Pro869Ser (c.2605C>T)?

AlphaMissense predicts likely benign (score 0.0634) — an in-silico prediction, not a clinical call.

ABL1 p.Pro869Ser

c.2605C>T · rs551509763 · VCV1995596

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0634	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -5.73	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 -0.63	GERP -0.46
Regional constraint	o/e 0.93	unconstrained · MANE · 5,156 bp · p 0.054 · regional, not allelic
Overall
CADD	3.042	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 0.00221% South Asian · 2/90,554 alleles

Filtering AF 0.000367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000186% 3/1,609,102 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00221%	45,277
African / African-American	0.00133%	74,970

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.Pro869Ser
Coding: c.2605C>T
MANE Select: NM_005157
dbSNP: rs551509763
Type: single nucleotide variant
Location: chr9:130884895 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 869: the 'disordered' region; the 'dna-binding' region

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

Similar variants

ABL1 p.Pro869= Likely 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-pro869ser (accessed [today's date]).

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