Is CSDE1 p.Ser74= (c.222A>G) pathogenic?

CSDE1 p.Ser74= (c.222A>G) is classified Likely benign in CSDE1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-08-18). Ultra-rare (popmax 0.0329%, mid); Associated with CSDE1-related disorder.

What condition is associated with CSDE1 p.Ser74= (c.222A>G)?

CSDE1 p.Ser74= (c.222A>G) is associated with CSDE1-related disorder (ClinVar).

How common is CSDE1 p.Ser74= (c.222A>G) in the general population?

CSDE1 p.Ser74= (c.222A>G) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

CSDE1 p.Ser74=

c.222A>G · rs759237728 · VCV3050575

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

CSDE1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.69	GERP -1.9, phastCons 1
Overall
CADD	10.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.00223% 36/1,613,650 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
South Asian	0.0296%	3,373
Remaining individualsnot grpmax-eligible	0.0048%	20,821
European (non-Finnish)	0.000339%	294,911

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.Ser74=
Coding: c.222A>G
MANE Select: NM_001007553
dbSNP: rs759237728
Type: single nucleotide variant
Location: chr1:114738050 (GRCh38)
Gene constraint: LOEUF 0.295 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.05 · 5 PDB
Residue 74: the csd 1 domain; a β-strand

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

Disease context

CSDE1-related disorder

Similar variants

CSDE1 p.Gln712Ter Likely pathogenic ★ same condition
CSDE1 p.Arg324Ter Uncertain significance ★ same condition
CSDE1 p.Arg774His Uncertain significance ★ ⚠ same condition
CSDE1 p.Met1Val Uncertain significance ★ same condition
CSDE1 p.Pro779Arg Uncertain significance ★ ⚠ same condition
CSDE1 p.Arg77Ter Uncertain significance same condition
CSDE1 p.Asp644Tyr Uncertain significance ⚠ same condition
CSDE1 c.2052+8C>T Likely benign 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-ser74 (accessed [today's date]).

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