Is CDAN1 p.Val866Ala (c.2597T>C) pathogenic?

CDAN1 p.Val866Ala (c.2597T>C) is classified Uncertain significance in CDAN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). AlphaMissense: likely pathogenic (0.5865); Very rare (popmax 0.00223%, eas); Associated with anemia, congenital dyserythropoietic, type 1a.

What condition is associated with CDAN1 p.Val866Ala (c.2597T>C)?

CDAN1 p.Val866Ala (c.2597T>C) is associated with anemia, congenital dyserythropoietic, type 1a (ClinVar).

How common is CDAN1 p.Val866Ala (c.2597T>C) in the general population?

CDAN1 p.Val866Ala (c.2597T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Congenital dyserythropoietic anemia type I inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CDAN1 p.Val866Ala (c.2597T>C)?

AlphaMissense predicts likely pathogenic (score 0.5865) — an in-silico prediction, not a clinical call.

CDAN1 p.Val866Ala

c.2597T>C · VCV4685998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5865 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

anemia, congenital dyserythropoietic, type 1a

Computational evidence

Protein change
AlphaMissense	0.5865	likely pathogenic
REVEL	0.819	moderately pathogenic-leaning
SaProt	LLR -9.85	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 11	GERP 2, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 7,202 bp · p 0.0016 · regional, not allelic
Overall
CADD	24.4	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 0.00223% East Asian · 1/44,870 alleles

Overall 6.84e-05% 1/1,461,892 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: CDAN1
Protein: p.Val866Ala
Coding: c.2597T>C
MANE Select: NM_138477
Type: single nucleotide variant
Location: chr15:42729071 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.58 · 2 PDB

Full CDAN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

anemia, congenital dyserythropoietic, type 1a — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital dyserythropoietic anemia type I (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

CDAN1 p.Val866Ile Uncertain significance ★★ ⚠ same residue
CDAN1 p.Val866= Likely benign ★★ same residue
CDAN1 p.Arg1042Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDAN1 p.Arg682Ter Pathogenic ★★ same condition
CDAN1 p.Arg714Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDAN1 p.Asn599Ser Likely pathogenic ★★ ⚠ same condition
CDAN1 p.Phe52Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDAN1 p.Pro1130Leu Pathogenic/Likely pathogenic ★★ 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/cdan1-p-val866ala (accessed [today's date]).

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