Is IPO7 p.His982Asp (c.2944C>G) pathogenic?

IPO7 p.His982Asp (c.2944C>G) is classified Uncertain significance in IPO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-23). AlphaMissense: likely benign (0.1195); Very rare (popmax 0.00102%, nfe).

How common is IPO7 p.His982Asp (c.2944C>G) in the general population?

IPO7 p.His982Asp (c.2944C>G) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about IPO7 p.His982Asp (c.2944C>G)?

AlphaMissense predicts likely benign (score 0.1195) — an in-silico prediction, not a clinical call.

IPO7 p.His982Asp

c.2944C>G · rs746207085 · VCV3110344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1195 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1195	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -4.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 3,979 bp · p 0.0034 · regional, not allelic
Overall
CADD	22.6	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 0.00102% European (non-Finnish) · 12/1,174,722 alleles

Filtering AF 0.000545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00043%

Overall 0.000746% 12/1,607,868 alleles · very rare exomes 11/1,455,776 · genomes 1/152,092 · joint denominator

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.His982Asp
Coding: c.2944C>G
MANE Select: NM_006391
dbSNP: rs746207085
Type: single nucleotide variant
Location: chr11:9442122 (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-his982asp (accessed [today's date]).

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