Is CSDE1 p.Val489Phe (c.1465G>T) pathogenic?

CSDE1 p.Val489Phe (c.1465G>T) is classified Uncertain significance in CSDE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely pathogenic (0.9602); Absent from gnomAD v4.1.

How common is CSDE1 p.Val489Phe (c.1465G>T) in the general population?

CSDE1 p.Val489Phe (c.1465G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSDE1 p.Val489Phe (c.1465G>T)?

AlphaMissense predicts likely pathogenic (score 0.9602) — an in-silico prediction, not a clinical call.

CSDE1 p.Val489Phe

c.1465G>T · VCV3367794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9602 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,603,642)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9602	likely pathogenic
REVEL	0.827	moderately pathogenic-leaning
SaProt	LLR -14.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.31	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 4,027 bp · p 0.77 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

No allele count reported in gnomAD v4.1 (AN 1,603,642). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CSDE1
Protein: p.Val489Phe
Coding: c.1465G>T
MANE Select: NM_001007553
Type: single nucleotide variant
Location: chr1:114726386 (GRCh38)
Gene constraint: LOEUF 0.295 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.05 · 5 PDB
Residue 489: the csd 6 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-val489phe (accessed [today's date]).

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