Is CDAN1 p.Pro268= (c.804C>A) pathogenic?

CDAN1 p.Pro268= (c.804C>A) is classified Benign/Likely benign in CDAN1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-01). Rare (popmax 0.275%, amr); Associated with anemia, congenital dyserythropoietic, type 1a.

What condition is associated with CDAN1 p.Pro268= (c.804C>A)?

CDAN1 p.Pro268= (c.804C>A) is associated with anemia, congenital dyserythropoietic, type 1a (ClinVar).

How common is CDAN1 p.Pro268= (c.804C>A) in the general population?

CDAN1 p.Pro268= (c.804C>A) is rare (popmax 0.275%, amr) (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.Pro268=

c.804C>A · rs191624595 · VCV2054884

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.275%, amr)

Conditions

anemia, congenital dyserythropoietic, type 1a

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.3	GERP -4.6
Overall
CADD	0.337	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.275% Admixed American · 165/60,026 alleles

Filtering AF 0.241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.228%

Overall 0.0171% 276/1,614,076 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.275%	364
Remaining individualsnot grpmax-eligible	0.0432%	2,315
African / African-American	0.0133%	7,502
European (non-Finnish)	0.00593%	16,857
East Asian	0.00223%	44,882
South Asian	0.0022%	45,540
Finnishnot grpmax-eligible	0.00156%	63,964

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.Pro268=
Coding: c.804C>A
MANE Select: NM_138477
dbSNP: rs191624595
Type: single nucleotide variant
Location: chr15:42735649 (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 268: the 'disordered' region

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.Pro268Arg Uncertain significance ★★ ⚠ same residue
CDAN1 p.Pro268Ser 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

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-pro268 (accessed [today's date]).

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