Is CDAN1 p.Pro186= (c.558C>G) pathogenic?

CDAN1 p.Pro186= (c.558C>G) is classified Benign/Likely benign in CDAN1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Common (popmax 18.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with congenital dyserythropoietic anemia type 1.

What condition is associated with CDAN1 p.Pro186= (c.558C>G)?

CDAN1 p.Pro186= (c.558C>G) is associated with congenital dyserythropoietic anemia type 1, anemia, congenital dyserythropoietic, type 1a (ClinVar).

How is Congenital dyserythropoietic anemia type I inherited?

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

CDAN1 p.Pro186=

Q: How common is CDAN1 p.Pro186= (c.558C>G) in the general population?

CDAN1 p.Pro186= (c.558C>G) is common (popmax 18.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.558C>G · rs12594325 · VCV262379

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 18.2%, afr) — too common for a highly-penetrant pathogenic allele

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 -1.2	GERP -3.9
Overall
CADD	5.488	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.2% African / African-American · 13,610/74,962 alleles

Filtering AF 17.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.8%

Overall 1.66% 26,837/1,612,410 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.2%	6
East Asian	5.2%	19
Ashkenazi Jewishnot grpmax-eligible	3.2%	31
South Asian	2.87%	35
Remaining individualsnot grpmax-eligible	2.18%	46
Middle Eastern	1.62%	62
Admixed American	1.39%	72
European (non-Finnish)	0.425%	235
Finnishnot grpmax-eligible	0.0347%	2,886

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.Pro186=
Coding: c.558C>G
MANE Select: NM_138477
dbSNP: rs12594325
Type: single nucleotide variant
Location: chr15:42736313 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.58 · 2 PDB
Residue 186: the 'disordered' region

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

Also linked: anemia, congenital dyserythropoietic, type 1a

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.Pro186Arg Uncertain significance ★ ⚠ 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
CDAN1 p.Pro51Leu 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-pro186 (accessed [today's date]).

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