Is IGF1 p.Cys95= (c.285C>T) pathogenic?

IGF1 p.Cys95= (c.285C>T) is classified Likely benign in IGF1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-01). Rare (popmax 0.528%, mid); Associated with growth delay due to insulin-like growth factor type 1 deficiency.

What condition is associated with IGF1 p.Cys95= (c.285C>T)?

IGF1 p.Cys95= (c.285C>T) is associated with growth delay due to insulin-like growth factor type 1 deficiency (ClinVar).

How common is IGF1 p.Cys95= (c.285C>T) in the general population?

IGF1 p.Cys95= (c.285C>T) is rare (popmax 0.528%, mid) (gnomAD).

IGF1 p.Cys95=

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.285C>T · rs3730193 · VCV731380

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.528%, mid)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP -0.096, phastCons 1
Overall
CADD	9.378	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.528% Middle Eastern · 32/6,062 alleles

Filtering AF 0.384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.335%

Overall 0.0379% 611/1,613,644 alleles · rare exomes 557/1,461,386 · genomes 54/152,258 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.528%	189
Ashkenazi Jewishnot grpmax-eligible	0.496%	201
South Asian	0.135%	740
Remaining individualsnot grpmax-eligible	0.0592%	1,689
Admixed American	0.04%	2,500
European (non-Finnish)	0.0205%	4,876
African / African-American	0.008%	12,505

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.Cys95=
Coding: c.285C>T
MANE Select: NM_000618
dbSNP: rs3730193
Type: single nucleotide variant
Location: chr12:102419626 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI 0.76 (gnomAD)
Structure: AlphaFold pLDDT 59.69 · 32 PDB
Residue 95: a disulfide bond; an α-helix; the 'a' 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-cys95 (accessed [today's date]).

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