Is ABL1 p.Arg516Cys (c.1546C>T) pathogenic?

ABL1 p.Arg516Cys (c.1546C>T) is classified Likely benign in ABL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-14). AlphaMissense: likely benign (0.1055); Very rare (popmax 0.00334%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABL1 p.Arg516Cys (c.1546C>T)?

ABL1 p.Arg516Cys (c.1546C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABL1 p.Arg516Cys (c.1546C>T) in the general population?

ABL1 p.Arg516Cys (c.1546C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about ABL1 p.Arg516Cys (c.1546C>T)?

AlphaMissense predicts likely benign (score 0.1055) — an in-silico prediction, not a clinical call.

ABL1 p.Arg516Cys

c.1546C>T · rs759795929 · VCV2969707

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1055	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -7.93	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 2.6	GERP -1.4, phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 5,156 bp · p 0.054 · regional, not allelic
Overall
CADD	23.3	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 0.00334% Admixed American · 2/59,964 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00217% 35/1,613,818 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,982
South Asian	0.00329%	30,357
African / African-American	0.00267%	37,447
European (non-Finnish)	0.00229%	43,701
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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.Arg516Cys
Coding: c.1546C>T
MANE Select: NM_005157
dbSNP: rs759795929
Type: single nucleotide variant
Location: chr9:130880532 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABL1 p.Arg516His Uncertain significance ★ ⚠ same residue
ABL1 p.Ala767Val Uncertain significance ★★ ⚠ same condition
ABL1 p.Arg1016His Uncertain significance ★★ ⚠ same condition
ABL1 p.Arg771Gly Uncertain significance ★★ ⚠ same condition
ABL1 p.Asn1088His Uncertain significance ★★ ⚠ same condition
ABL1 p.Asn120Thr Uncertain significance ★★ ⚠ same condition
ABL1 p.Asn414Lys Uncertain significance ★★ ⚠ same condition
ABL1 p.Glu123Gln Uncertain significance ★★ ⚠ 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-arg516cys (accessed [today's date]).

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