Is CDAN1 p.Pro1128= (c.3384G>A) pathogenic?

CDAN1 p.Pro1128= (c.3384G>A) is classified Conflicting classifications of pathogenicity in CDAN1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-24). Very rare (popmax 0.00891%, eas); Associated with congenital dyserythropoietic anemia type 1.

What condition is associated with CDAN1 p.Pro1128= (c.3384G>A)?

CDAN1 p.Pro1128= (c.3384G>A) is associated with congenital dyserythropoietic anemia type 1 (ClinVar).

How common is CDAN1 p.Pro1128= (c.3384G>A) in the general population?

CDAN1 p.Pro1128= (c.3384G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

How is Congenital dyserythropoietic anemia type I inherited?

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

CDAN1 p.Pro1128=

c.3384G>A · rs141832648 · VCV315920

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

congenital dyserythropoietic anemia type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.1
Overall
CADD	0.082	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,882 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00502% 81/1,614,058 alleles · very rare exomes 77/1,461,892 · genomes 4/152,166 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.159%	630
Remaining individualsnot grpmax-eligible	0.0128%	7,811
East Asiangrpmax	0.00891%	11,220
Admixed American	0.00333%	30,001
South Asian	0.0022%	45,546
European (non-Finnish)	0.00144%	69,415
African / African-American	0.00133%	74,914

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1128=
Coding: c.3384G>A
MANE Select: NM_138477
dbSNP: rs141832648
Type: single nucleotide variant
Location: chr15:42725555 (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

congenital dyserythropoietic anemia type 1 — 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.Pro1128Leu Uncertain significance ★★ ⚠ same residue
CDAN1 p.Arg1042Trp Pathogenic/Likely 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
CDAN1 p.Pro51Leu Likely pathogenic ★★ ⚠ same condition
CDAN1 p.Pro672Leu 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-pro1128 (accessed [today's date]).

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