Is CBLL1 p.Arg487Lys (c.1460G>A) pathogenic?

CBLL1 p.Arg487Lys (c.1460G>A) is classified Uncertain significance in CBLL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-18). AlphaMissense: likely pathogenic (0.6535); Absent from gnomAD v4.1.

How common is CBLL1 p.Arg487Lys (c.1460G>A) in the general population?

CBLL1 p.Arg487Lys (c.1460G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBLL1 p.Arg487Lys (c.1460G>A)?

AlphaMissense predicts likely pathogenic (score 0.6535) — an in-silico prediction, not a clinical call.

CBLL1 p.Arg487Lys

c.1460G>A · rs564621638 · VCV2255742

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6535 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6535	likely pathogenic
REVEL	0.233	benign-leaning
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 577 bp · p 0.11 · 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CBLL1
Protein: p.Arg487Lys
Coding: c.1460G>A
MANE Select: NM_024814
dbSNP: rs564621638
Type: single nucleotide variant
Location: chr7:107759162 (GRCh38)
Gene constraint: LOEUF 0.251 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.68
Residue 487: the 'disordered' region

Full CBLL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBLL1 p.Arg487Ser Uncertain significance ★ ⚠ same residue
CBLL1 p.Ala38Val Uncertain significance ★ ⚠ same type
CBLL1 p.Ala418Val Uncertain significance ★ ⚠ same type
CBLL1 p.Ala41Pro Uncertain significance ★ ⚠ same type
CBLL1 p.Ala41Val Uncertain significance ★ ⚠ same type
CBLL1 p.Arg24Lys Uncertain significance ★ ⚠ same type
CBLL1 p.Arg261His Uncertain significance ★ ⚠ same type
CBLL1 p.Arg46Gly Uncertain significance ★ ⚠ 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/cbll1-p-arg487lys (accessed [today's date]).

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