Is CUEDC2 p.Arg202Lys (c.605G>A) pathogenic?

CUEDC2 p.Arg202Lys (c.605G>A) is classified Uncertain significance in CUEDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.0898); Ultra-rare (popmax 0.037%, nfe).

How common is CUEDC2 p.Arg202Lys (c.605G>A) in the general population?

CUEDC2 p.Arg202Lys (c.605G>A) is ultra-rare (popmax 0.037%, nfe) (gnomAD).

What do computational predictors say about CUEDC2 p.Arg202Lys (c.605G>A)?

AlphaMissense predicts likely benign (score 0.0898) — an in-silico prediction, not a clinical call.

CUEDC2 p.Arg202Lys

c.605G>A · rs369567008 · VCV2520555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0898 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.037%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0898	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -6.52	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 0.81	GERP 1.6, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 1,759 bp · p 2.4e-07 · regional, not allelic
Overall
CADD	17.47	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 0.037% European (non-Finnish) · 437/1,179,766 alleles

Filtering AF 0.0342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.0285% 459/1,613,254 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.037%	2,700
Remaining individualsnot grpmax-eligible	0.016%	6,244
African / African-American	0.012%	8,325
Admixed American	0.005%	19,984

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.Arg202Lys
Coding: c.605G>A
MANE Select: NM_024040
dbSNP: rs369567008
Type: single nucleotide variant
Location: chr10:102423849 (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.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
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-arg202lys (accessed [today's date]).

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