Is IPO7 p.Asp425Gly (c.1274A>G) pathogenic?

IPO7 p.Asp425Gly (c.1274A>G) is classified Uncertain significance in IPO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-31). AlphaMissense: likely pathogenic (0.6658); Very rare (popmax 0.00401%, afr).

How common is IPO7 p.Asp425Gly (c.1274A>G) in the general population?

IPO7 p.Asp425Gly (c.1274A>G) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about IPO7 p.Asp425Gly (c.1274A>G)?

AlphaMissense predicts likely pathogenic (score 0.6658) — an in-silico prediction, not a clinical call.

IPO7 p.Asp425Gly

c.1274A>G · VCV3286320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6658 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6658	likely pathogenic
REVEL	0.659	pathogenic-leaning
SaProt	LLR -11.83	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 6,071 bp · p 1.6e-10 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00401% African / African-American · 3/74,864 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000558% 9/1,612,244 alleles · very rare exomes 7/1,460,082 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,955
Remaining individualsnot grpmax-eligible	0.0016%	62,338
South Asian	0.0011%	90,996
European (non-Finnish)	0.000339%	294,860

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.Asp425Gly
Coding: c.1274A>G
MANE Select: NM_006391
Type: single nucleotide variant
Location: chr11:9425201 (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-asp425gly (accessed [today's date]).

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