Is IGF2 p.Arg64Cys (c.190C>T) pathogenic?

IGF2 p.Arg64Cys (c.190C>T) is classified Uncertain significance in IGF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely pathogenic (0.7508); Very rare (popmax 0.00333%, amr).

How common is IGF2 p.Arg64Cys (c.190C>T) in the general population?

IGF2 p.Arg64Cys (c.190C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about IGF2 p.Arg64Cys (c.190C>T)?

AlphaMissense predicts likely pathogenic (score 0.7508) — an in-silico prediction, not a clinical call.

IGF2 p.Arg64Cys

c.190C>T · rs762200142 · VCV1478636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7508 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.7508	likely pathogenic
REVEL	0.81	moderately pathogenic-leaning
SaProt	LLR -14.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.8	GERP -0.15, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 1,851 bp · p 3.2e-08 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00333% Admixed American · 2/59,990 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000682% 11/1,612,916 alleles · very rare exomes 10/1,460,720 · genomes 1/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,995
African / African-American	0.00267%	37,460
European (non-Finnish)	0.000593%	168,573

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: IGF2
Protein: p.Arg64Cys
Coding: c.190C>T
MANE Select: NM_000612
dbSNP: rs762200142
Type: single nucleotide variant
Location: chr11:2133633 (GRCh38)

Full IGF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/igf2-p-arg64cys (accessed [today's date]).

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