Is IGF2 p.Ala88Pro (c.262G>C) pathogenic?

IGF2 p.Ala88Pro (c.262G>C) is classified Uncertain significance in IGF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-20). AlphaMissense: likely benign (0.2657); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with IGF2 p.Ala88Pro (c.262G>C)?

IGF2 p.Ala88Pro (c.262G>C) is associated with Inborn genetic diseases (ClinVar).

How common is IGF2 p.Ala88Pro (c.262G>C) in the general population?

IGF2 p.Ala88Pro (c.262G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IGF2 p.Ala88Pro (c.262G>C)?

AlphaMissense predicts likely benign (score 0.2657) — an in-silico prediction, not a clinical call.

IGF2 p.Ala88Pro

c.262G>C · VCV3528039

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2657 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2657	likely benign
REVEL	0.42	indeterminate
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.034, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 600 bp · p 0.33 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: IGF2
Protein: p.Ala88Pro
Coding: c.262G>C
MANE Select: NM_000612
Type: single nucleotide variant
Location: chr11:2133561 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 58.95 · 16 PDB
Residue 88: a UniProt-annotated variant site (in srs3); a β-strand; the 'd' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IGF2 p.Ala167Ser Uncertain significance ★★ ⚠ same condition
IGF2 p.Arg154Cys Uncertain significance ★★ ⚠ same condition
IGF2 p.Arg156Cys Uncertain significance ★★ ⚠ same condition
IGF2 p.Arg64His Uncertain significance ★★ ⚠ same condition
IGF2 p.Asp165Glu Uncertain significance ★★ ⚠ same condition
IGF2 p.Gly139Val Uncertain significance ★★ ⚠ same condition
IGF2 p.Met1Thr Uncertain significance ★★ same condition
IGF2 p.Thr82Met Uncertain significance ★★ ⚠ 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/igf2-p-ala88pro (accessed [today's date]).

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