Is IGF2R p.Pro772Ser (c.2314C>T) pathogenic?

IGF2R p.Pro772Ser (c.2314C>T) is classified Uncertain significance in IGF2R (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-06). AlphaMissense: likely benign (0.0954); Rare (popmax 0.125%, afr).

How common is IGF2R p.Pro772Ser (c.2314C>T) in the general population?

IGF2R p.Pro772Ser (c.2314C>T) is rare (popmax 0.125%, afr) (gnomAD).

What do computational predictors say about IGF2R p.Pro772Ser (c.2314C>T)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

IGF2R p.Pro772Ser

c.2314C>T · rs77985420 · VCV2375779

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.125%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP 1.4, phastCons 0.6
Regional constraint	o/e 0.97	unconstrained · MANE · 79 kb · p 0.39 · regional, not allelic
Overall
CADD	21.4	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 0.125% African / African-American · 94/75,016 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0971%

Overall 0.00657% 106/1,613,454 alleles · rare exomes 55/1,461,186 · genomes 51/152,268 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.125%	798
Admixed American	0.00833%	12,002
Remaining individualsnot grpmax-eligible	0.008%	12,500
European (non-Finnish)	0.00017%	589,689

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.Pro772Ser
Coding: c.2314C>T
MANE Select: NM_000876
dbSNP: rs77985420
Type: single nucleotide variant
Location: chr6:160047876 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.48 · 24 PDB
Residue 772: the mrh 6 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-pro772ser (accessed [today's date]).

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