Is IPO8 p.Pro37Leu (c.110C>T) pathogenic?

IPO8 p.Pro37Leu (c.110C>T) is classified Uncertain significance in IPO8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely pathogenic (0.8623); No allele count reported in gnomAD v4.1 (AN 1,589,046); Associated with Inborn genetic diseases.

What condition is associated with IPO8 p.Pro37Leu (c.110C>T)?

IPO8 p.Pro37Leu (c.110C>T) is associated with Inborn genetic diseases (ClinVar).

How common is IPO8 p.Pro37Leu (c.110C>T) in the general population?

IPO8 p.Pro37Leu (c.110C>T) is no allele count reported in gnomAD v4.1 (AN 1,589,046) (gnomAD).

What do computational predictors say about IPO8 p.Pro37Leu (c.110C>T)?

AlphaMissense predicts likely pathogenic (score 0.8623) — an in-silico prediction, not a clinical call.

IPO8 p.Pro37Leu

c.110C>T · VCV3529626

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8623 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,589,046)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8623	likely pathogenic
REVEL	0.346	indeterminate
SaProt	LLR -9.38	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 6,146 bp · p 7.4e-06 · regional, not allelic
Overall
CADD	28.7	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

No allele count reported in gnomAD v4.1 (AN 1,589,046). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: IPO8
Protein: p.Pro37Leu
Coding: c.110C>T
MANE Select: NM_006390
Type: single nucleotide variant
Location: chr12:30690552 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 87.59
Residue 37: the importin n-terminal domain; a UniProt-annotated variant site (in viss; undetectable protein levels in either patient's fibroblasts or patient's epstein-barr virus-immortalized b cell lines)

Full IPO8 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

IPO8 p.Ala877Asp Uncertain significance ★★ ⚠ same condition
IPO8 p.Ala941Val Uncertain significance ★★ ⚠ same condition
IPO8 p.Arg1002Trp Uncertain significance ★★ ⚠ same condition
IPO8 p.Arg884Gln Uncertain significance ★★ ⚠ same condition
IPO8 p.Asn953Asp Uncertain significance ★★ ⚠ same condition
IPO8 p.His435Arg Uncertain significance ★★ ⚠ same condition
IPO8 p.Lys533Asn Uncertain significance ★★ ⚠ same condition
IPO8 p.Pro423Leu 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/ipo8-p-pro37leu (accessed [today's date]).

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