Is IGF2BP2 p.Pro391Ser (c.1171C>T) pathogenic?

IGF2BP2 p.Pro391Ser (c.1171C>T) is classified Uncertain significance in IGF2BP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-08). AlphaMissense: likely benign (0.0579); Ultra-rare (popmax 0.025%, amr).

How common is IGF2BP2 p.Pro391Ser (c.1171C>T) in the general population?

IGF2BP2 p.Pro391Ser (c.1171C>T) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about IGF2BP2 p.Pro391Ser (c.1171C>T)?

AlphaMissense predicts likely benign (score 0.0579) — an in-silico prediction, not a clinical call.

IGF2BP2 p.Pro391Ser

c.1171C>T · rs748920710 · VCV3108543

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0579 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0579	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.3	GERP 0.58, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 15 kb · p 0.36 · regional, not allelic
Overall
CADD	19.97	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 0.025% Admixed American · 15/59,938 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0125%

Overall 0.00552% 89/1,612,540 alleles · ultra-rare exomes 81/1,460,452 · genomes 8/152,088 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	3,996
Remaining individualsnot grpmax-eligible	0.0112%	8,915
European (non-Finnish)	0.00551%	18,141
African / African-American	0.00267%	37,439

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: IGF2BP2
Protein: p.Pro391Ser
Coding: c.1171C>T
MANE Select: NM_006548
dbSNP: rs748920710
Type: single nucleotide variant
Location: chr3:185672570 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.70 · 4 PDB

Full IGF2BP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IGF2BP2 p.Ala103Val Uncertain significance ★ ⚠ same type
IGF2BP2 p.Ala16Thr Uncertain significance ★ ⚠ same type
IGF2BP2 p.Ala182Thr Uncertain significance ★ ⚠ same type
IGF2BP2 p.Ala31Glu Uncertain significance ★ ⚠ same type
IGF2BP2 p.Ala348Thr Uncertain significance ★ ⚠ same type
IGF2BP2 p.Ala394Val Uncertain significance ★ ⚠ same type
IGF2BP2 p.Ala441Thr Uncertain significance ★ ⚠ same type
IGF2BP2 p.Ala512Val 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/igf2bp2-p-pro391ser (accessed [today's date]).

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