Is IPO7 p.Thr390Ile (c.1169C>T) pathogenic?

IPO7 p.Thr390Ile (c.1169C>T) is classified Uncertain significance in IPO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). AlphaMissense: ambiguous (0.4897); Ultra-rare (popmax 0.0342%, mid).

How common is IPO7 p.Thr390Ile (c.1169C>T) in the general population?

IPO7 p.Thr390Ile (c.1169C>T) is ultra-rare (popmax 0.0342%, mid) (gnomAD).

What do computational predictors say about IPO7 p.Thr390Ile (c.1169C>T)?

AlphaMissense predicts ambiguous (score 0.4897) — an in-silico prediction, not a clinical call.

IPO7 p.Thr390Ile

c.1169C>T · VCV3529613

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4897 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0342%, mid)

Computational evidence

Protein change
AlphaMissense	0.4897	ambiguous
REVEL	0.362	indeterminate
SaProt	LLR -7.83	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 6,071 bp · p 1.6e-10 · regional, not allelic
Overall
CADD	24.8	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 0.0342% Middle Eastern · 2/5,852 alleles

Filtering AF 0.00601% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00249%

Overall 0.000881% 14/1,589,888 alleles · ultra-rare exomes 12/1,437,702 · genomes 2/152,186 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0342%	2,926
Remaining individualsnot grpmax-eligible	0.00812%	12,308
Admixed American	0.00186%	53,722
African / African-American	0.00136%	73,334
European (non-Finnish)	0.000427%	234,034

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: IPO7
Protein: p.Thr390Ile
Coding: c.1169C>T
MANE Select: NM_006391
Type: single nucleotide variant
Location: chr11:9424941 (GRCh38)
Gene constraint: LOEUF 0.138 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.24

Full IPO7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IPO7 p.Ala363Gly Uncertain significance ★ ⚠ same type
IPO7 p.Ala74Ser Uncertain significance ★ ⚠ same type
IPO7 p.Ala764Gly Uncertain significance ★ ⚠ same type
IPO7 p.Ala786Gly Uncertain significance ★ ⚠ same type
IPO7 p.Ala843Ser Uncertain significance ★ ⚠ same type
IPO7 p.Ala923Gly Uncertain significance ★ ⚠ same type
IPO7 p.Ala979Thr Uncertain significance ★ ⚠ same type
IPO7 p.Arg125His 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/ipo7-p-thr390ile (accessed [today's date]).

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