Is CBLL1 p.Ala41Val (c.122C>T) pathogenic?

CBLL1 p.Ala41Val (c.122C>T) is classified Uncertain significance in CBLL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.0663); Absent from gnomAD v4.1.

How common is CBLL1 p.Ala41Val (c.122C>T) in the general population?

CBLL1 p.Ala41Val (c.122C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBLL1 p.Ala41Val (c.122C>T)?

AlphaMissense predicts likely benign (score 0.0663) — an in-silico prediction, not a clinical call.

CBLL1 p.Ala41Val

c.122C>T · VCV3485666

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0663 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0663	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -6.57	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 0.84	GERP -2, phastCons 0.97
Regional constraint	o/e 1.03	unconstrained · MANE · 14 kb · p 0.67 · regional, not allelic
Overall
CADD	16.28	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Ala41Val
Coding: c.122C>T
MANE Select: NM_024814
Type: single nucleotide variant
Location: chr7:107748988 (GRCh38)
Gene constraint: LOEUF 0.251 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.68
Residue 41: the 'disordered' region

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

Similar variants

CBLL1 p.Ala41Pro Uncertain significance ★ ⚠ same residue
CBLL1 p.Ala38Val Uncertain significance ★ ⚠ same type
CBLL1 p.Ala418Val 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
CBLL1 p.Arg487Lys Uncertain significance ★ ⚠ same type
CBLL1 p.Arg487Ser 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-ala41val (accessed [today's date]).

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