Is CBL p.Ala310Val (c.929C>T) pathogenic?

CBL p.Ala310Val (c.929C>T) is classified Conflicting classifications of pathogenicity in CBL (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-26). AlphaMissense: ambiguous (0.3445); Ultra-rare (popmax 0.0178%, eas); Associated with RASopathy.

What condition is associated with CBL p.Ala310Val (c.929C>T)?

CBL p.Ala310Val (c.929C>T) is associated with RASopathy (ClinVar).

How common is CBL p.Ala310Val (c.929C>T) in the general population?

CBL p.Ala310Val (c.929C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about CBL p.Ala310Val (c.929C>T)?

AlphaMissense predicts ambiguous (score 0.3445) — an in-silico prediction, not a clinical call.

CBL p.Ala310Val

c.929C>T · rs764199611 · VCV1502497

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3445 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

RASopathy

Computational evidence

Protein change
AlphaMissense	0.3445	ambiguous
REVEL	0.475	indeterminate
SaProt	LLR -11.06	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.2, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 45 kb · p 4.6e-13 · regional, not allelic
Overall
CADD	27.6	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 0.0178% East Asian · 8/44,902 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000496% 8/1,613,366 alleles · ultra-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: CBL
Protein: p.Ala310Val
Coding: c.929C>T
MANE Select: NM_005188
dbSNP: rs764199611
Type: single nucleotide variant
Location: chr11:119276056 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.27 · 34 PDB
Residue 310: the cbl-ptb domain; the 'sufficient for interaction with ephb1' region; the 'sh2-like' region; a turn

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

Disease context

RASopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CBL p.Ala310Gly Uncertain significance ★ ⚠ same residue
CBL p.Ala310Asp Uncertain significance ★ ⚠ same residue
CBL p.Ala310Thr Uncertain significance ★ ⚠ same residue
CBL c.1096-1G>C Pathogenic/Likely pathogenic ★★ same condition
CBL c.1096-1G>T Pathogenic ★★ same condition
CBL c.1228-2A>G Pathogenic/Likely pathogenic ★★ same condition
CBL p.Arg420Gln Pathogenic/Likely pathogenic ★★ same condition
CBL p.Arg420Leu 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/cbl-p-ala310val (accessed [today's date]).

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