Is CUEDC2 p.Arg233Trp (c.697C>T) pathogenic?

CUEDC2 p.Arg233Trp (c.697C>T) is classified Uncertain significance in CUEDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). AlphaMissense: ambiguous (0.374); Very rare (popmax 0.00668%, eas).

How common is CUEDC2 p.Arg233Trp (c.697C>T) in the general population?

CUEDC2 p.Arg233Trp (c.697C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about CUEDC2 p.Arg233Trp (c.697C>T)?

AlphaMissense predicts ambiguous (score 0.374) — an in-silico prediction, not a clinical call.

CUEDC2 p.Arg233Trp

c.697C>T · VCV3270306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.374 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.374	ambiguous
REVEL	0.753	pathogenic-leaning
SaProt	LLR -13.52	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 0.6, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 1,759 bp · p 2.4e-07 · regional, not allelic
Overall
CADD	27.9	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 0.00668% East Asian · 3/44,886 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00164% 24/1,461,874 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,962
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.00153%	65,557
South Asian	0.0011%	91,086

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: CUEDC2
Protein: p.Arg233Trp
Coding: c.697C>T
MANE Select: NM_024040
Type: single nucleotide variant
Location: chr10:102423677 (GRCh38)
Gene constraint: LOEUF 0.457 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82

Full CUEDC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CUEDC2 p.Arg233Gln Uncertain significance ★ ⚠ same residue
CUEDC2 p.Ala226Ser Uncertain significance ★ ⚠ same type
CUEDC2 p.Ala56Val Uncertain significance ★ ⚠ same type
CUEDC2 p.Ala69Thr Uncertain significance ★ ⚠ same type
CUEDC2 p.Ala9Val Uncertain significance ★ ⚠ same type
CUEDC2 p.Arg116Gln Uncertain significance ★ ⚠ same type
CUEDC2 p.Arg116Trp Uncertain significance ★ ⚠ same type
CUEDC2 p.Arg172Trp Uncertain significance ★ ⚠ 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/cuedc2-p-arg233trp (accessed [today's date]).

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