Is IGF1 p.Pro50= (c.150G>A) pathogenic?

IGF1 p.Pro50= (c.150G>A) is classified Conflicting classifications of pathogenicity in IGF1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-01). Ultra-rare (popmax 0.0171%, nfe); Associated with growth delay due to insulin-like growth factor type 1 deficiency.

What condition is associated with IGF1 p.Pro50= (c.150G>A)?

IGF1 p.Pro50= (c.150G>A) is associated with growth delay due to insulin-like growth factor type 1 deficiency (ClinVar).

How common is IGF1 p.Pro50= (c.150G>A) in the general population?

IGF1 p.Pro50= (c.150G>A) is ultra-rare (popmax 0.0171%, nfe) (gnomAD).

IGF1 p.Pro50=

Q: How is Growth delay due to insulin-like growth factor type 1 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.150G>A · rs373202198 · VCV880615

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, nfe)

Conditions

growth delay due to insulin-like growth factor type 1 deficiency

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 -15	GERP -3.7
Overall
CADD	0.386	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0171% European (non-Finnish) · 202/1,180,048 alleles

Filtering AF 0.0152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0144%

Overall 0.0133% 215/1,614,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0171%	5,842
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Admixed American	0.005%	20,003
East Asian	0.00446%	22,446
African / African-American	0.004%	24,975
South Asian	0.0011%	91,084

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: IGF1
Protein: p.Pro50=
Coding: c.150G>A
MANE Select: NM_000618
dbSNP: rs373202198
Type: single nucleotide variant
Location: chr12:102475713 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI 0.76 (gnomAD)
Structure: AlphaFold pLDDT 59.69 · 32 PDB
Residue 50: the 'b' region

Full IGF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

growth delay due to insulin-like growth factor type 1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Growth delay due to insulin-like growth factor type 1 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

IGF1 c.*260A>T Uncertain significance ★★ same condition
IGF1 c.*105T>C Likely benign ★★ same condition
IGF1 c.*1770C>T Benign ★★ same condition
IGF1 c.*2364A>G Benign ★★ same condition
IGF1 c.*259A>T Likely benign ★★ same condition
IGF1 c.*261A>T Benign ★★ same condition
IGF1 c.*263T>A Benign/Likely benign ★★ same condition
IGF1 c.*3226C>G Benign ★★ 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/igf1-p-pro50 (accessed [today's date]).

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