Is IGF1 p.Ala36Val (c.107C>T) pathogenic?

IGF1 p.Ala36Val (c.107C>T) is classified Uncertain significance in IGF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.0771); Ultra-rare (popmax 0.0111%, eas); Associated with growth delay due to insulin-like growth factor type 1 deficiency.

What condition is associated with IGF1 p.Ala36Val (c.107C>T)?

IGF1 p.Ala36Val (c.107C>T) is associated with growth delay due to insulin-like growth factor type 1 deficiency (ClinVar).

How common is IGF1 p.Ala36Val (c.107C>T) in the general population?

IGF1 p.Ala36Val (c.107C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about IGF1 p.Ala36Val (c.107C>T)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

IGF1 p.Ala36Val

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.107C>T · rs775312813 · VCV306908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.7	GERP -2.1, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 61 kb · p 3.2e-08 · regional, not allelic
Overall
CADD	18.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,890 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000991% 16/1,614,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,978
African / African-American	0.00267%	37,462
Finnishnot grpmax-eligible	0.00156%	64,042
European (non-Finnish)	0.000678%	147,505

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.Ala36Val
Coding: c.107C>T
dbSNP: rs775312813
Type: single nucleotide variant
Location: chr12:102475756 (GRCh38)

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

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-ala36val (accessed [today's date]).

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