Is CSDE1 p.Leu400Phe (c.1198C>T) pathogenic?

CSDE1 p.Leu400Phe (c.1198C>T) is classified Likely benign in CSDE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-06). AlphaMissense: likely pathogenic (0.6929); Absent from gnomAD v4.1.

How common is CSDE1 p.Leu400Phe (c.1198C>T) in the general population?

CSDE1 p.Leu400Phe (c.1198C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSDE1 p.Leu400Phe (c.1198C>T)?

AlphaMissense predicts likely pathogenic (score 0.6929) — an in-silico prediction, not a clinical call.

CSDE1 p.Leu400Phe

c.1198C>T · rs2101033296 · VCV1302066

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6929 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6929	likely pathogenic
REVEL	0.156	moderately benign-leaning
SaProt	LLR -5.24	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 3,722 bp · p 6.9e-09 · regional, not allelic
Overall
CADD	26.9	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.Leu400Phe
Coding: c.1198C>T
MANE Select: NM_001007553
dbSNP: rs2101033296
Type: single nucleotide variant
Location: chr1:114730416 (GRCh38)
Gene constraint: LOEUF 0.295 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.05 · 5 PDB
Residue 400: the csd 5 domain; a β-strand

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-leu400phe (accessed [today's date]).

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