Is CSDE1 p.Arg99Gln (c.296G>A) pathogenic?

CSDE1 p.Arg99Gln (c.296G>A) is classified Uncertain significance in CSDE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely benign (0.1263); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with CSDE1 p.Arg99Gln (c.296G>A)?

CSDE1 p.Arg99Gln (c.296G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CSDE1 p.Arg99Gln (c.296G>A) in the general population?

CSDE1 p.Arg99Gln (c.296G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CSDE1 p.Arg99Gln (c.296G>A)?

AlphaMissense predicts likely benign (score 0.1263) — an in-silico prediction, not a clinical call.

CSDE1 p.Arg99Gln

c.296G>A · rs2524829855 · VCV3077965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1263 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1263	likely benign
REVEL	0.332	indeterminate
SaProt	LLR -10.95	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 2.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 3,579 bp · p 0.21 · regional, not allelic
Overall
CADD	27.6	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 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00237%

Overall 0.00308% 45/1,459,572 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
European (non-Finnish)	0.00357%	28,046
East Asian	0.00223%	44,870
Remaining individualsnot grpmax-eligible	0.0016%	62,448

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: CSDE1
Protein: p.Arg99Gln
Coding: c.296G>A
MANE Select: NM_001007553
dbSNP: rs2524829855
Type: single nucleotide variant
Location: chr1:114737976 (GRCh38)
Gene constraint: LOEUF 0.295 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.05 · 5 PDB

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-arg99gln (accessed [today's date]).

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