Is CSDE1 p.Arg774His (c.2321G>A) pathogenic?

CSDE1 p.Arg774His (c.2321G>A) is classified Uncertain significance in CSDE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely pathogenic (0.6632); Very rare (popmax 0.00134%, afr); Associated with CSDE1-related disorder.

What condition is associated with CSDE1 p.Arg774His (c.2321G>A)?

CSDE1 p.Arg774His (c.2321G>A) is associated with CSDE1-related disorder (ClinVar).

How common is CSDE1 p.Arg774His (c.2321G>A) in the general population?

CSDE1 p.Arg774His (c.2321G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CSDE1 p.Arg774His (c.2321G>A)?

AlphaMissense predicts likely pathogenic (score 0.6632) — an in-silico prediction, not a clinical call.

CSDE1 p.Arg774His

c.2321G>A · rs1375202283 · VCV2631456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6632 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CSDE1-related disorder

Computational evidence

Protein change
AlphaMissense	0.6632	likely pathogenic
REVEL	0.681	pathogenic-leaning
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -1.2, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 8,076 bp · p 4.1e-12 · regional, not allelic
Overall
CADD	28.9	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

Grpmax group 0.00134% African / African-American · 1/74,902 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,972 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,902
European (non-Finnish)	0.000169%	590,012

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.Arg774His
Coding: c.2321G>A
MANE Select: NM_001007553
dbSNP: rs1375202283
Type: single nucleotide variant
Location: chr1:114718641 (GRCh38)
Gene constraint: LOEUF 0.295 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.05 · 5 PDB
Residue 774: the suz-c domain

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

Disease context

CSDE1-related disorder

Similar variants

CSDE1 p.Arg774Cys Uncertain significance ★ ⚠ same residue
CSDE1 p.Gln712Ter Likely pathogenic ★ same condition
CSDE1 p.Arg324Ter Uncertain significance ★ same condition
CSDE1 p.Met1Val Uncertain significance ★ same condition
CSDE1 p.Pro779Arg Uncertain significance ★ ⚠ same condition
CSDE1 p.Arg77Ter Uncertain significance same condition
CSDE1 p.Asp644Tyr Uncertain significance ⚠ same condition
CSDE1 c.2052+8C>T Likely benign 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-arg774his (accessed [today's date]).

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