Is CSDE1 p.Met561Val (c.1681A>G) pathogenic?

CSDE1 p.Met561Val (c.1681A>G) is classified Uncertain significance in CSDE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely benign (0.0766); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with CSDE1 p.Met561Val (c.1681A>G)?

CSDE1 p.Met561Val (c.1681A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CSDE1 p.Met561Val (c.1681A>G) in the general population?

CSDE1 p.Met561Val (c.1681A>G) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about CSDE1 p.Met561Val (c.1681A>G)?

AlphaMissense predicts likely benign (score 0.0766) — an in-silico prediction, not a clinical call.

CSDE1 p.Met561Val

c.1681A>G · VCV3836658

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0766 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0766	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -4.64	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 0.62	unconstrained · MANE · 8,076 bp · p 4.1e-12 · regional, not allelic
Overall
CADD	20.5	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 0.00439% South Asian · 4/91,088 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000496% 8/1,614,084 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,772
African / African-American	0.004%	24,979
European (non-Finnish)	8.47e-05%	1,180,040

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.Met561Val
Coding: c.1681A>G
MANE Select: NM_001007553
Type: single nucleotide variant
Location: chr1:114725293 (GRCh38)
Gene constraint: LOEUF 0.295 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.05 · 5 PDB
Residue 561: a β-strand; the csd 7 domain

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.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
CSDE1 c.1-1687A>G 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-met561val (accessed [today's date]).

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