Is IGF2 p.Val44Ile (c.130G>A) pathogenic?

IGF2 p.Val44Ile (c.130G>A) is classified Uncertain significance in IGF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-21). AlphaMissense: likely benign (0.1903); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with IGF2 p.Val44Ile (c.130G>A)?

IGF2 p.Val44Ile (c.130G>A) is associated with Inborn genetic diseases (ClinVar).

How common is IGF2 p.Val44Ile (c.130G>A) in the general population?

IGF2 p.Val44Ile (c.130G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about IGF2 p.Val44Ile (c.130G>A)?

AlphaMissense predicts likely benign (score 0.1903) — an in-silico prediction, not a clinical call.

IGF2 p.Val44Ile

c.130G>A · rs747135996 · VCV3108530

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1903	likely benign
REVEL	0.693	pathogenic-leaning
SaProt	LLR -9.26	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 1,851 bp · p 3.2e-08 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 0.00446% East Asian · 2/44,876 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00149% 24/1,613,418 alleles · very rare exomes 24/1,461,076 · genomes 0/152,342 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,438
South Asian	0.00439%	22,760
European (non-Finnish)	0.00153%	65,544

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: IGF2
Protein: p.Val44Ile
Coding: c.130G>A
MANE Select: NM_000612
dbSNP: rs747135996
Type: single nucleotide variant
Location: chr11:2135394 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 58.95 · 16 PDB
Residue 44: a UniProt-annotated variant site (in srs3); an α-helix; the 'b' 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-val44ile (accessed [today's date]).

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