Is CSDE1 p.Leu139Val (c.415C>G) pathogenic?

CSDE1 p.Leu139Val (c.415C>G) is classified Uncertain significance in CSDE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-15). AlphaMissense: ambiguous (0.4213); Very rare (popmax 8.5e-05%, nfe).

How common is CSDE1 p.Leu139Val (c.415C>G) in the general population?

CSDE1 p.Leu139Val (c.415C>G) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about CSDE1 p.Leu139Val (c.415C>G)?

AlphaMissense predicts ambiguous (score 0.4213) — an in-silico prediction, not a clinical call.

CSDE1 p.Leu139Val

c.415C>G · VCV4282190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4213 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4213	ambiguous
REVEL	0.565	indeterminate
SaProt	LLR -2.65	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 3,579 bp · p 0.21 · regional, not allelic
Overall
CADD	23.6	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 8.5e-05% European (non-Finnish) · 1/1,176,696 alleles

Overall 6.86e-05% 1/1,457,170 alleles · very rare

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.Leu139Val
Coding: c.415C>G
MANE Select: NM_001007553
Type: single nucleotide variant
Location: chr1:114736843 (GRCh38)
Gene constraint: LOEUF 0.295 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.05 · 5 PDB
Residue 139: the csd 2; truncated domain

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

Similar variants

CSDE1 p.Ala765Thr Uncertain significance ★★ ⚠ same type
CSDE1 p.Arg132His Uncertain significance ★★ ⚠ same type
CSDE1 p.Glu335Gly Uncertain significance ★★ ⚠ same type
CSDE1 c.2053-4T>C Benign/Likely benign ★★ same type
CSDE1 c.2350-5C>A Benign/Likely benign ★★ same type
CSDE1 p.Phe699= Benign/Likely benign ★★ same type
CSDE1 p.Ser75= Benign ★★ same type
CSDE1 c.500+1G>C 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/csde1-p-leu139val (accessed [today's date]).

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