Is CSDE1 p.Cys733Phe (c.2198G>T) pathogenic?

CSDE1 p.Cys733Phe (c.2198G>T) is classified Uncertain significance in CSDE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely pathogenic (0.8663); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CSDE1 p.Cys733Phe (c.2198G>T)?

CSDE1 p.Cys733Phe (c.2198G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CSDE1 p.Cys733Phe (c.2198G>T) in the general population?

CSDE1 p.Cys733Phe (c.2198G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSDE1 p.Cys733Phe (c.2198G>T)?

AlphaMissense predicts likely pathogenic (score 0.8663) — an in-silico prediction, not a clinical call.

CSDE1 p.Cys733Phe

c.2198G>T · VCV4007294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8663 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8663	likely pathogenic
REVEL	0.875	moderately pathogenic-leaning
SaProt	LLR -9.32	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 8,076 bp · p 4.1e-12 · regional, not allelic
Overall
CADD	26.5	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

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: CSDE1
Protein: p.Cys733Phe
Coding: c.2198G>T
MANE Select: NM_001007553
Type: single nucleotide variant
Location: chr1:114719597 (GRCh38)
Gene constraint: LOEUF 0.295 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.05 · 5 PDB
Residue 733: the csd 9 domain

Full CSDE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSDE1 p.Ala765Thr Uncertain significance ★★ ⚠ same condition
CSDE1 p.Arg132His Uncertain significance ★★ ⚠ same condition
CSDE1 p.Glu335Gly Uncertain significance ★★ ⚠ same condition
CSDE1 c.2350-5C>A Benign/Likely benign ★★ same condition
CSDE1 p.Ile200Phe Likely pathogenic ★ same condition
CSDE1 c.1-1653C>G Uncertain significance ★ same condition
CSDE1 c.1-1661G>C Uncertain significance ★ same condition
CSDE1 c.1-1687A>G Uncertain significance ★ same condition

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/csde1-p-cys733phe (accessed [today's date]).

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