Is IGF1R p.Phe820= (c.2460C>T) pathogenic?

IGF1R p.Phe820= (c.2460C>T) is classified Conflicting classifications of pathogenicity in IGF1R (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-29). Ultra-rare (popmax 0.0167%, mid); Associated with growth delay due to insulin-like growth factor I resistance.

What condition is associated with IGF1R p.Phe820= (c.2460C>T)?

IGF1R p.Phe820= (c.2460C>T) is associated with growth delay due to insulin-like growth factor I resistance (ClinVar).

How common is IGF1R p.Phe820= (c.2460C>T) in the general population?

IGF1R p.Phe820= (c.2460C>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

IGF1R p.Phe820=

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.2460C>T · rs769964962 · VCV885703

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

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 -3.7	GERP -4.2
Overall
CADD	1.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Middle Eastern · 1/5,998 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00174% 28/1,612,848 alleles · ultra-rare exomes 27/1,460,596 · genomes 1/152,252 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,998
European (non-Finnish)	0.00195%	51,306
Admixed American	0.00167%	60,016
Remaining individualsnot grpmax-eligible	0.0016%	62,452
African / African-American	0.00133%	74,940
South Asian	0.0011%	91,066

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.Phe820=
Coding: c.2460C>T
MANE Select: NM_000875
dbSNP: rs769964962
Type: single nucleotide variant
Location: chr15:98922406 (GRCh38)
Gene constraint: LOEUF 0.393 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 46 PDB
Residue 820: the fibronectin type-iii 3 domain

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.Phe820Leu Uncertain significance ★ ⚠ same residue
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

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-phe820 (accessed [today's date]).

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