Is IPO7 p.Arg805Cys (c.2413C>T) pathogenic?

IPO7 p.Arg805Cys (c.2413C>T) is classified Uncertain significance in IPO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-07). AlphaMissense: likely benign (0.2224); Very rare (popmax 0.00534%, afr).

How common is IPO7 p.Arg805Cys (c.2413C>T) in the general population?

IPO7 p.Arg805Cys (c.2413C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about IPO7 p.Arg805Cys (c.2413C>T)?

AlphaMissense predicts likely benign (score 0.2224) — an in-silico prediction, not a clinical call.

IPO7 p.Arg805Cys

c.2413C>T · rs773555364 · VCV2322903

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2224 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2224	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -10.62	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 7,102 bp · p 0.00018 · regional, not allelic
Overall
CADD	28.7	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 0.00534% African / African-American · 4/74,892 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00105% 17/1,613,666 alleles · very rare exomes 15/1,461,536 · genomes 2/152,130 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,723
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
Admixed American	0.00333%	29,996
Remaining individualsnot grpmax-eligible	0.0032%	31,236
South Asian	0.0011%	91,062
European (non-Finnish)	0.000593%	168,538

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.Arg805Cys
Coding: c.2413C>T
MANE Select: NM_006391
dbSNP: rs773555364
Type: single nucleotide variant
Location: chr11:9437898 (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-arg805cys (accessed [today's date]).

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