Is CSDE1 p.Asn440Ser (c.1319A>G) pathogenic?

CSDE1 p.Asn440Ser (c.1319A>G) is classified Uncertain significance in CSDE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.0572); Ultra-rare (popmax 0.0312%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CSDE1 p.Asn440Ser (c.1319A>G)?

CSDE1 p.Asn440Ser (c.1319A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CSDE1 p.Asn440Ser (c.1319A>G) in the general population?

CSDE1 p.Asn440Ser (c.1319A>G) is ultra-rare (popmax 0.0312%, nfe) (gnomAD).

What do computational predictors say about CSDE1 p.Asn440Ser (c.1319A>G)?

AlphaMissense predicts likely benign (score 0.0572) — an in-silico prediction, not a clinical call.

CSDE1 p.Asn440Ser

c.1319A>G · rs149300730 · VCV2371492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0572 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0572	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -4.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 4,027 bp · p 0.77 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0312% European (non-Finnish) · 368/1,180,032 alleles

Filtering AF 0.0285% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0275%

Overall 0.0234% 377/1,614,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0312%	3,207
Remaining individualsnot grpmax-eligible	0.0128%	7,810
African / African-American	0.00133%	74,928

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.Asn440Ser
Coding: c.1319A>G
MANE Select: NM_001007553
dbSNP: rs149300730
Type: single nucleotide variant
Location: chr1:114730295 (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.Asn440His Uncertain significance ★ ⚠ same residue
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

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-asn440ser (accessed [today's date]).

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