Is IGF2R p.Leu730= (c.2190C>G) pathogenic?

IGF2R p.Leu730= (c.2190C>G) is classified Likely benign in IGF2R (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). Absent from gnomAD v4.1.

How common is IGF2R p.Leu730= (c.2190C>G) in the general population?

IGF2R p.Leu730= (c.2190C>G) is absent from gnomAD v4.1 (gnomAD).

IGF2R p.Leu730=

c.2190C>G · rs2483502611 · VCV2657102

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9	GERP -3.4
Overall
CADD	0.082	PHRED · no single calibrated threshold — expert panels disagree

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: IGF2R
Protein: p.Leu730=
Coding: c.2190C>G
MANE Select: NM_000876
dbSNP: rs2483502611
Type: single nucleotide variant
Location: chr6:160047297 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.48 · 24 PDB
Residue 730: a β-strand; the mrh 5 domain

Full IGF2R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IGF2R p.Asp2219= Benign/Likely benign ★★ same type
IGF2R p.Leu817Val Benign ★★ same type
IGF2R p.Pro2129= Benign/Likely benign ★★ same type
IGF2R p.His151Tyr Likely pathogenic ★ ⚠ same type
IGF2R c.289+2T>C Uncertain significance ★ same type
IGF2R p.Ala1033Pro Uncertain significance ★ ⚠ same type
IGF2R p.Ala104Thr Uncertain significance ★ ⚠ same type
IGF2R p.Ala1252Thr 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/igf2r-p-leu730 (accessed [today's date]).

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