Is CUEDC2 p.Ala56Val (c.167C>T) pathogenic?

CUEDC2 p.Ala56Val (c.167C>T) is classified Uncertain significance in CUEDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-17). AlphaMissense: likely benign (0.1615); Very rare (popmax 0.000254%, nfe).

How common is CUEDC2 p.Ala56Val (c.167C>T) in the general population?

CUEDC2 p.Ala56Val (c.167C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CUEDC2 p.Ala56Val (c.167C>T)?

AlphaMissense predicts likely benign (score 0.1615) — an in-silico prediction, not a clinical call.

CUEDC2 p.Ala56Val

c.167C>T · rs774191179 · VCV2267720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1615 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1615	likely benign
REVEL	0.216	benign-leaning
SaProt	LLR -9.28	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 9.9	GERP 2, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 1,759 bp · p 2.4e-07 · regional, not allelic
Overall
CADD	20.1	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 0.000254% European (non-Finnish) · 3/1,180,018 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,858 alleles · very rare

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.Ala56Val
Coding: c.167C>T
MANE Select: NM_024040
dbSNP: rs774191179
Type: single nucleotide variant
Location: chr10:102424700 (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.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.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-ala56val (accessed [today's date]).

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