Is ABL1 p.Ala647Asp (c.1940C>A) pathogenic?

ABL1 p.Ala647Asp (c.1940C>A) is classified Benign in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-26). AlphaMissense: likely benign (0.1542); Ultra-rare (popmax 0.0178%, eas).

How common is ABL1 p.Ala647Asp (c.1940C>A) in the general population?

ABL1 p.Ala647Asp (c.1940C>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about ABL1 p.Ala647Asp (c.1940C>A)?

AlphaMissense predicts likely benign (score 0.1542) — an in-silico prediction, not a clinical call.

ABL1 p.Ala647Asp

c.1940C>A · rs199694985 · VCV1989446

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1542 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1542	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.48	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 0.26	GERP -1.6
Regional constraint	o/e 0.93	unconstrained · MANE · 5,156 bp · p 0.054 · regional, not allelic
Overall
CADD	8.621	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 0.0178% East Asian · 8/44,844 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000619% 9/1,453,844 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,606
Remaining individualsnot grpmax-eligible	0.00161%	62,070

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.Ala647Asp
Coding: c.1940C>A
MANE Select: NM_005157
dbSNP: rs199694985
Type: single nucleotide variant
Location: chr9:130884230 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 647: the 'disordered' region

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

Similar variants

ABL1 p.Ala647Val Benign/Likely benign ★★ same residue
ABL1 p.Ala647Thr 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

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-ala647asp (accessed [today's date]).

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