Is CUEDC2 p.Arg116Trp (c.346C>T) pathogenic?

CUEDC2 p.Arg116Trp (c.346C>T) is classified Uncertain significance in CUEDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-20). AlphaMissense: likely benign (0.066); Rare (popmax 0.132%, mid).

How common is CUEDC2 p.Arg116Trp (c.346C>T) in the general population?

CUEDC2 p.Arg116Trp (c.346C>T) is rare (popmax 0.132%, mid) (gnomAD).

What do computational predictors say about CUEDC2 p.Arg116Trp (c.346C>T)?

AlphaMissense predicts likely benign (score 0.066) — an in-silico prediction, not a clinical call.

CUEDC2 p.Arg116Trp

c.346C>T · VCV3837435

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.066 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.066	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -9.03	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 0.25	GERP -3.6
Regional constraint	o/e 0.73	unconstrained · MANE · 1,759 bp · p 2.4e-07 · regional, not allelic
Overall
CADD	15.9	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 0.132% Middle Eastern · 8/6,062 alleles

Filtering AF 0.0656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.00985% 159/1,614,144 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	758
Remaining individualsnot grpmax-eligible	0.0224%	4,465
South Asian	0.0143%	7,006
European (non-Finnish)	0.00992%	10,086
African / African-American	0.00533%	18,760
Admixed American	0.005%	20,005

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.Arg116Trp
Coding: c.346C>T
MANE Select: NM_024040
Type: single nucleotide variant
Location: chr10:102424329 (GRCh38)
Gene constraint: LOEUF 0.457 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82
Residue 116: the 'disordered' region

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

Similar variants

CUEDC2 p.Arg116Gln 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.Arg172Trp Uncertain significance ★ ⚠ same type
CUEDC2 p.Arg202Lys Uncertain significance ★ ⚠ same type
CUEDC2 p.Arg233Gln 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-arg116trp (accessed [today's date]).

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