Is IGF2 p.Asp76fs (c.227del) pathogenic?

IGF2 p.Asp76fs (c.227del) is classified Likely pathogenic in IGF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-15). No gnomAD frequency available for this variant.

How common is IGF2 p.Asp76fs (c.227del) in the general population?

IGF2 p.Asp76fs (c.227del) is no gnomAD frequency available for this variant (gnomAD).

IGF2 p.Asp76fs

c.227del · rs2133585000 · VCV1275788

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.5	GERP -2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: IGF2
Protein: p.Asp76fs
Coding: c.227del
MANE Select: NM_000612
dbSNP: rs2133585000
Type: Deletion
Location: chr11:2133596 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 58.95 · 16 PDB
Residue 76: a UniProt-annotated variant site (in srs3); the 'a' region

Full IGF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IGF2 p.Pro157_Leu158insTer Uncertain significance ★★ same type
IGF2 p.Arg61_Arg62insTer Likely pathogenic ★ same type
IGF2 p.Glu30fs Pathogenic ★ same type
IGF2 p.Glu36fs Likely pathogenic ★ same type
IGF2 p.Ile66fs Likely pathogenic ★ same type
IGF2 c.158-20_158-17del Uncertain significance ★ same type
IGF2 p.Cys75fs Uncertain significance ★ same type
IGF2 p.Gly170fs 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/igf2-p-asp76fs (accessed [today's date]).

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