Is CBLC p.Gln272Arg (c.815A>G) pathogenic?

CBLC p.Gln272Arg (c.815A>G) is classified Uncertain significance in CBLC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: likely benign (0.1052); Absent from gnomAD v4.1.

How common is CBLC p.Gln272Arg (c.815A>G) in the general population?

CBLC p.Gln272Arg (c.815A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBLC p.Gln272Arg (c.815A>G)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

CBLC p.Gln272Arg

c.815A>G · VCV4219973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.443	indeterminate
SaProt	LLR -11.90	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP -0.32, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 19 kb · p 0.99 · regional, not allelic
Overall
CADD	21.6	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

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: CBLC
Protein: p.Gln272Arg
Coding: c.815A>G
MANE Select: NM_012116
Type: single nucleotide variant
Location: chr19:44784299 (GRCh38)
Gene constraint: LOEUF 1.058 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.85 · 7 PDB
Residue 272: the cbl-ptb domain; the 'sh2-like' region

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

Similar variants

CBLC p.Ala122Ser Uncertain significance ★ ⚠ same type
CBLC p.Ala137Val Uncertain significance ★ ⚠ same type
CBLC p.Ala21Val Uncertain significance ★ ⚠ same type
CBLC p.Ala377Pro Uncertain significance ★ ⚠ same type
CBLC p.Ala398Val Uncertain significance ★ ⚠ same type
CBLC p.Ala433Ser Uncertain significance ★ ⚠ same type
CBLC p.Ala450Gly Uncertain significance ★ ⚠ same type
CBLC p.Ala465Val 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/cblc-p-gln272arg (accessed [today's date]).

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