Is ABL1 p.Ser679Ala (c.2035T>G) pathogenic?

ABL1 p.Ser679Ala (c.2035T>G) is classified Benign/Likely benign in ABL1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.0594); Rare (popmax 0.149%, mid); Associated with congenital heart defects and skeletal malformations syndrome.

How common is ABL1 p.Ser679Ala (c.2035T>G) in the general population?

ABL1 p.Ser679Ala (c.2035T>G) is rare (popmax 0.149%, mid) (gnomAD).

What do computational predictors say about ABL1 p.Ser679Ala (c.2035T>G)?

AlphaMissense predicts likely benign (score 0.0594) — an in-silico prediction, not a clinical call.

ABL1 p.Ser679Ala

Q: What condition is associated with ABL1 p.Ser679Ala (c.2035T>G)?

ABL1 p.Ser679Ala (c.2035T>G) is associated with congenital heart defects and skeletal malformations syndrome, chronic myeloid leukemia (ClinVar).

c.2035T>G · rs201278085 · VCV1594971

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0594 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.149%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital heart defects and skeletal malformations syndrome

Computational evidence

Protein change
AlphaMissense	0.0594	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -6.78	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 -1.9	GERP -2.1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,156 bp · p 0.054 · regional, not allelic
Overall
CADD	0.519	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 0.149% Middle Eastern · 9/6,046 alleles

Filtering AF 0.0776% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.058%

Overall 0.033% 532/1,611,856 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.149%	672
Ashkenazi Jewishnot grpmax-eligible	0.101%	986
Admixed American	0.0617%	1,620
Remaining individualsnot grpmax-eligible	0.0593%	1,687
European (non-Finnish)	0.0348%	2,877
South Asian	0.00659%	15,174
African / African-American	0.00267%	37,508
Finnishnot grpmax-eligible	0.0016%	62,648

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.Ser679Ala
Coding: c.2035T>G
MANE Select: NM_005157
dbSNP: rs201278085
Type: single nucleotide variant
Location: chr9:130884325 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 679: the 'disordered' region

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

Disease context

congenital heart defects and skeletal malformations syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: chronic myeloid leukemia

For Marfanoid habitus-facial dysmorphism-skeletal abnormality-heart defect syndrome (Orphanet):

Onset: Neonatal

Similar variants

ABL1 p.Ser679Thr Likely benign ★ same residue
ABL1 p.Ala337Thr Pathogenic ★★ ⚠ same condition
ABL1 p.Ala433Thr Likely pathogenic ★★ same condition
ABL1 p.Asp504Gly Likely pathogenic ★★ ⚠ same condition
ABL1 p.Glu509Lys Pathogenic/Likely pathogenic ★★ same condition
ABL1 p.Gly254Arg Pathogenic/Likely pathogenic ★★ same condition
ABL1 p.Pro230Leu Likely pathogenic ★★ same condition
ABL1 p.Trp99Arg Likely pathogenic ★★ 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-ser679ala (accessed [today's date]).

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