Is ABL1 p.Ser977Arg (c.2931C>G) pathogenic?

ABL1 p.Ser977Arg (c.2931C>G) is classified Likely benign in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: ambiguous (0.447); Very rare (popmax 8.47e-05%, nfe).

How common is ABL1 p.Ser977Arg (c.2931C>G) in the general population?

ABL1 p.Ser977Arg (c.2931C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ABL1 p.Ser977Arg (c.2931C>G)?

AlphaMissense predicts ambiguous (score 0.447) — an in-silico prediction, not a clinical call.

ABL1 p.Ser977Arg

c.2931C>G · rs1228313826 · VCV2976326

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.447 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.447	ambiguous
REVEL	0.045	moderately benign-leaning
SaProt	LLR -7.61	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,156 bp · p 0.054 · regional, not allelic
Overall
CADD	19.5	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 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 6.84e-05% 1/1,461,420 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.Ser977Arg
Coding: c.2931C>G
MANE Select: NM_005157
dbSNP: rs1228313826
Type: single nucleotide variant
Location: chr9:130885221 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 977: the 'disordered' region; a modified residue (phosphoserine); the 'f-actin-binding' region

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

Similar variants

ABL1 p.Ser977Gly Uncertain significance ★ ⚠ same residue
ABL1 p.Ser977Asn 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-ser977arg (accessed [today's date]).

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