Is IPO7 p.Leu342Val (c.1024C>G) pathogenic?

IPO7 p.Leu342Val (c.1024C>G) is classified Uncertain significance in IPO7 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-08). AlphaMissense: likely benign (0.2752); Ultra-rare (popmax 0.0441%, sas).

How common is IPO7 p.Leu342Val (c.1024C>G) in the general population?

IPO7 p.Leu342Val (c.1024C>G) is ultra-rare (popmax 0.0441%, sas) (gnomAD).

What do computational predictors say about IPO7 p.Leu342Val (c.1024C>G)?

AlphaMissense predicts likely benign (score 0.2752) — an in-silico prediction, not a clinical call.

IPO7 p.Leu342Val

c.1024C>G · VCV4378174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2752 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0441%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2752	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	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	25.0	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 0.0441% South Asian · 39/88,488 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00279% 44/1,575,950 alleles · ultra-rare exomes 44/1,423,678 · genomes 0/152,272 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0441%	2,269
Remaining individualsnot grpmax-eligible	0.00656%	15,238
East Asian	0.00224%	44,626

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.Leu342Val
Coding: c.1024C>G
MANE Select: NM_006391
Type: single nucleotide variant
Location: chr11:9423123 (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-leu342val (accessed [today's date]).

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