Is CBLIF p.Val346del (c.1032TGT[1]) pathogenic?

CBLIF p.Val346del (c.1032TGT[1]) is classified Uncertain significance in CBLIF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-09). Very rare (popmax 0.00133%, afr).

How common is CBLIF p.Val346del (c.1032TGT[1]) in the general population?

CBLIF p.Val346del (c.1032TGT[1]) is very rare (popmax 0.00133%, afr) (gnomAD).

CBLIF p.Val346del

c.1032TGT[1] · rs762845250 · VCV2683151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.62	GERP -0.1, phastCons 0.99

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,030 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00109% 16/1,461,738 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
African / African-Americangrpmax	0.00133%	75,030
European (non-Finnish)	0.00119%	84,279

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CBLIF
Protein: p.Val346del
Coding: c.1032TGT[1]
MANE Select: NM_005142
dbSNP: rs762845250
Type: Microsatellite
Location: chr11:59835844 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69 · 2 PDB
Residue 346: an α-helix

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

Similar variants

CBLIF p.Lys145del Conflicting classifications of pathogenicity ★ same type
CBLIF c.1192+179TA[11] Benign ★ same type
CBLIF c.1192+179TA[9] Benign ★ same type
CBLIF c.79+10_79+12del Likely benign ★ 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/cblif-p-val346del (accessed [today's date]).

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