Is IQSEC2 p.Arg795Pro (c.2384G>C) pathogenic?

IQSEC2 p.Arg795Pro (c.2384G>C) is classified Uncertain significance in IQSEC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1.

How common is IQSEC2 p.Arg795Pro (c.2384G>C) in the general population?

IQSEC2 p.Arg795Pro (c.2384G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IQSEC2 p.Arg795Pro (c.2384G>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

IQSEC2 p.Arg795Pro

c.2384G>C · rs2147089214 · VCV3251025

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 1% in IQSEC2
REVEL	0.686	pathogenic-leaning
SaProt	LLR -17.11	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 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.04	constrained · MANE · 583 bp · p 2.5e-07 · regional, not allelic
Overall
CADD	33.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IQSEC2
Protein: p.Arg795Pro
Coding: c.2384G>C
MANE Select: NM_001111125
dbSNP: rs2147089214
Type: single nucleotide variant
Location: chrX:53248796 (GRCh38)
Structure: AlphaFold pLDDT 54.46 · 2 PDB
Residue 795: the sec7 domain

Full IQSEC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IQSEC2 p.Arg795Gln Uncertain significance ★ ⚠ same residue
IQSEC2 p.Arg795Trp Uncertain significance ★ ⚠ same residue
IQSEC2 c.2459+21C>T Pathogenic ★★ same type
IQSEC2 c.2889+1G>A Pathogenic ★★ same type
IQSEC2 p.Ala836Val Pathogenic/Likely pathogenic ★★ same type
IQSEC2 p.Arg1055Ter Pathogenic ★★ same type
IQSEC2 p.Arg1145Ter Pathogenic ★★ same type
IQSEC2 p.Arg359His Likely pathogenic ★★ 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/iqsec2-p-arg795pro (accessed [today's date]).

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