Is IPO7 p.Val108Leu (c.322G>T) pathogenic?

IPO7 p.Val108Leu (c.322G>T) is classified Uncertain significance in IPO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely pathogenic (0.6294); Very rare (popmax 0.00218%, nfe).

How common is IPO7 p.Val108Leu (c.322G>T) in the general population?

IPO7 p.Val108Leu (c.322G>T) is very rare (popmax 0.00218%, nfe) (gnomAD).

What do computational predictors say about IPO7 p.Val108Leu (c.322G>T)?

AlphaMissense predicts likely pathogenic (score 0.6294) — an in-silico prediction, not a clinical call.

IPO7 p.Val108Leu

c.322G>T · VCV3860960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6294 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00218%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6294	likely pathogenic
REVEL	0.297	indeterminate
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 15 kb · p 0.24 · regional, not allelic
Overall
CADD	28.2	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 0.00218% European (non-Finnish) · 25/1,147,002 alleles

Filtering AF 0.0015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00126%

Overall 0.00169% 26/1,539,440 alleles · very rare exomes 25/1,387,730 · genomes 1/151,710 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00218%	45,880
Remaining individualsnot grpmax-eligible	0.00169%	59,046

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.Val108Leu
Coding: c.322G>T
MANE Select: NM_006391
Type: single nucleotide variant
Location: chr11:9409929 (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-val108leu (accessed [today's date]).

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