Is ITM2B p.Pro30Ser (c.88C>T) pathogenic?

ITM2B p.Pro30Ser (c.88C>T) is classified Conflicting classifications of pathogenicity in ITM2B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-12). AlphaMissense: likely benign (0.1536); Rare (popmax 0.304%, amr); Associated with Inborn genetic diseases.

What condition is associated with ITM2B p.Pro30Ser (c.88C>T)?

ITM2B p.Pro30Ser (c.88C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ITM2B p.Pro30Ser (c.88C>T) in the general population?

ITM2B p.Pro30Ser (c.88C>T) is rare (popmax 0.304%, amr) (gnomAD).

What do computational predictors say about ITM2B p.Pro30Ser (c.88C>T)?

AlphaMissense predicts likely benign (score 0.1536) — an in-silico prediction, not a clinical call.

ITM2B p.Pro30Ser

c.88C>T · rs769773974 · VCV1670992

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1536 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.304%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1536	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -6.73	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 4.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 28 kb · p 0.069 · regional, not allelic
Overall
CADD	19.89	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.304% Admixed American · 151/49,700 alleles

Filtering AF 0.264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.249%

Overall 0.0102% 157/1,536,996 alleles · rare exomes 57/1,384,910 · genomes 100/152,086 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.304%	329
Middle Eastern	0.0169%	5,912
Remaining individualsnot grpmax-eligible	0.00674%	14,834
European (non-Finnish)	8.75e-05%	1,143,413

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: ITM2B
Protein: p.Pro30Ser
Coding: c.88C>T
MANE Select: NM_021999
dbSNP: rs769773974
Type: single nucleotide variant
Location: chr13:48233448 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI 0.58 (gnomAD)
Structure: AlphaFold pLDDT 76.31 · 2 PDB

Full ITM2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITM2B p.Pro30Thr Uncertain significance ★ ⚠ same residue
ITM2B p.Pro30Leu Uncertain significance ★ ⚠ same residue
ITM2B p.Pro30= Likely benign ★ same residue
ITM2B p.Arg233Cys Uncertain significance ★★ ⚠ same condition
ITM2B p.Asp85Asn Uncertain significance ★★ ⚠ same condition
ITM2B p.Glu126Val Uncertain significance ★★ ⚠ same condition
ITM2B p.His200Asp Uncertain significance ★★ ⚠ same condition
ITM2B p.Ile240Val Uncertain significance ★★ ⚠ same condition

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/itm2b-p-pro30ser (accessed [today's date]).

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