Is IGF1R p.Phe75= (c.225C>T) pathogenic?

IGF1R p.Phe75= (c.225C>T) is classified Benign/Likely benign in IGF1R (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-11). Rare (popmax 0.452%, nfe); Associated with growth delay due to insulin-like growth factor I resistance.

What condition is associated with IGF1R p.Phe75= (c.225C>T)?

IGF1R p.Phe75= (c.225C>T) is associated with growth delay due to insulin-like growth factor I resistance (ClinVar).

How common is IGF1R p.Phe75= (c.225C>T) in the general population?

IGF1R p.Phe75= (c.225C>T) is rare (popmax 0.452%, nfe) (gnomAD).

IGF1R p.Phe75=

Q: How is Growth delay due to insulin-like growth factor I resistance inherited?

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

c.225C>T · rs55770488 · VCV281171

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.452%, nfe)

Conditions

growth delay due to insulin-like growth factor I resistance

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 0.18	GERP -0.76, phastCons 0.97
Overall
CADD	8.099	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.452% European (non-Finnish) · 5,332/1,180,030 alleles

Filtering AF 0.442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.438%

Overall 0.371% 5,986/1,614,178 alleles · rare exomes 5,532/1,461,892 · genomes 454/152,286 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.452%	221
Remaining individualsnot grpmax-eligible	0.318%	314
Finnishnot grpmax-eligible	0.237%	421
Admixed American	0.195%	513
South Asian	0.11%	911
Middle Eastern	0.099%	1,010
African / African-American	0.0813%	1,230
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,742
East Asian	0.00446%	22,439

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: IGF1R
Protein: p.Phe75=
Coding: c.225C>T
MANE Select: NM_000875
dbSNP: rs55770488
Type: single nucleotide variant
Location: chr15:98707692 (GRCh38)
Gene constraint: LOEUF 0.393 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 46 PDB

Full IGF1R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Growth delay due to insulin-like growth factor I resistance (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

IGF1R p.Arg365Ter Pathogenic/Likely pathogenic ★★ same condition
IGF1R p.Arg753Ter Pathogenic/Likely pathogenic ★★ same condition
IGF1R p.Gly1152Arg Pathogenic/Likely pathogenic ★★ same condition
IGF1R c.*3338G>A Uncertain significance ★★ same condition
IGF1R p.Ala1309Thr Uncertain significance ★★ ⚠ same condition
IGF1R p.Ala578Thr Uncertain significance ★★ ⚠ same condition
IGF1R p.Arg1139Trp Uncertain significance ★★ ⚠ same condition
IGF1R p.Arg1158Gln 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/igf1r-p-phe75 (accessed [today's date]).

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