Is IGF2R p.Ser201= (c.603C>T) pathogenic?

IGF2R p.Ser201= (c.603C>T) is classified Likely benign in IGF2R (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). Rare (popmax 0.68%, nfe).

How common is IGF2R p.Ser201= (c.603C>T) in the general population?

IGF2R p.Ser201= (c.603C>T) is rare (popmax 0.68%, nfe) (gnomAD).

IGF2R p.Ser201=

c.603C>T · rs11759563 · VCV2657098

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.68%, nfe)

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 -6.4	GERP -3.2
Overall
CADD	4.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.68% European (non-Finnish) · 8,020/1,179,946 alleles

Filtering AF 0.667% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.662%

Overall 0.682% 11,015/1,614,012 alleles · rare exomes 10,053/1,461,810 · genomes 962/152,202 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.64%	27
Amishnot grpmax-eligible	1.21%	83
European (non-Finnish)grpmax	0.68%	147
Remaining individualsnot grpmax-eligible	0.565%	177
African / African-American	0.132%	758
South Asian	0.127%	785
Admixed American	0.105%	953
Middle Eastern	0.066%	1,516
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,277
East Asian	0.0134%	7,480

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: IGF2R
Protein: p.Ser201=
Coding: c.603C>T
MANE Select: NM_000876
dbSNP: rs11759563
Type: single nucleotide variant
Location: chr6:160024661 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.48 · 24 PDB
Residue 201: the mrh 2 domain

Full IGF2R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IGF2R p.Asp2219= Benign/Likely benign ★★ same type
IGF2R p.Leu817Val Benign ★★ same type
IGF2R p.Pro2129= Benign/Likely benign ★★ same type
IGF2R p.His151Tyr Likely pathogenic ★ ⚠ same type
IGF2R c.289+2T>C Uncertain significance ★ same type
IGF2R p.Ala1033Pro Uncertain significance ★ ⚠ same type
IGF2R p.Ala104Thr Uncertain significance ★ ⚠ same type
IGF2R p.Ala1252Thr Uncertain significance ★ ⚠ same type

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/igf2r-p-ser201 (accessed [today's date]).

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