Is IGF1 p.Ser30= (c.90G>A) pathogenic?

IGF1 p.Ser30= (c.90G>A) is classified Conflicting classifications of pathogenicity in IGF1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-12). Ultra-rare (popmax 0.0233%, amr); Associated with growth delay due to insulin-like growth factor type 1 deficiency.

What condition is associated with IGF1 p.Ser30= (c.90G>A)?

IGF1 p.Ser30= (c.90G>A) is associated with growth delay due to insulin-like growth factor type 1 deficiency (ClinVar).

How common is IGF1 p.Ser30= (c.90G>A) in the general population?

IGF1 p.Ser30= (c.90G>A) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

IGF1 p.Ser30=

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.90G>A · rs374228630 · VCV880616

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

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 -5.3	GERP -3.5
Overall
CADD	4.286	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0233% Admixed American · 14/59,972 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.0039% 63/1,613,792 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,284
African / African-American	0.00668%	14,976
European (non-Finnish)	0.00373%	26,817

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.Ser30=
Coding: c.90G>A
MANE Select: NM_000618
dbSNP: rs374228630
Type: single nucleotide variant
Location: chr12:102475773 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI 0.76 (gnomAD)
Structure: AlphaFold pLDDT 59.69 · 32 PDB

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-ser30 (accessed [today's date]).

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