Is CDAN1 p.Arg1007Trp (c.3019C>T) pathogenic?

CDAN1 p.Arg1007Trp (c.3019C>T) is classified Uncertain significance in CDAN1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-01-08). AlphaMissense: likely benign (0.0788); Ultra-rare (popmax 0.0889%, sas); Associated with anemia, congenital dyserythropoietic, type 1a.

What condition is associated with CDAN1 p.Arg1007Trp (c.3019C>T)?

CDAN1 p.Arg1007Trp (c.3019C>T) is associated with anemia, congenital dyserythropoietic, type 1a, congenital dyserythropoietic anemia type 1 (ClinVar).

How common is CDAN1 p.Arg1007Trp (c.3019C>T) in the general population?

CDAN1 p.Arg1007Trp (c.3019C>T) is ultra-rare (popmax 0.0889%, sas) (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.Arg1007Trp (c.3019C>T)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

CDAN1 p.Arg1007Trp

c.3019C>T · rs142276684 · VCV886002

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0889%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

anemia, congenital dyserythropoietic, type 1a

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.418	indeterminate
SaProt	LLR -8.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.2, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 7,202 bp · p 0.0016 · regional, not allelic
Overall
CADD	26.1	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 0.0889% South Asian · 78/87,778 alleles

Filtering AF 0.0729% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0671%

Overall 0.0107% 169/1,584,490 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0889%	1,125
Middle Eastern	0.0507%	1,973
Remaining individualsnot grpmax-eligible	0.0115%	8,731
European (non-Finnish)	0.00654%	15,280
African / African-American	0.00538%	18,605
East Asian	0.00226%	44,320

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.Arg1007Trp
Coding: c.3019C>T
MANE Select: NM_138477
dbSNP: rs142276684
Type: single nucleotide variant
Location: chr15:42727698 (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

Also linked: congenital dyserythropoietic anemia type 1

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.Arg1007Pro Uncertain significance ★ ⚠ same residue
CDAN1 p.Arg1007= 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-arg1007trp (accessed [today's date]).

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