Is CDAN1 p.Pro672= (c.2016G>A) pathogenic?

CDAN1 p.Pro672= (c.2016G>A) is classified Conflicting classifications of pathogenicity in CDAN1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-03). Ultra-rare (popmax 0.0291%, nfe); Associated with congenital dyserythropoietic anemia type 1.

What condition is associated with CDAN1 p.Pro672= (c.2016G>A)?

CDAN1 p.Pro672= (c.2016G>A) is associated with congenital dyserythropoietic anemia type 1, anemia, congenital dyserythropoietic, type 1a (ClinVar).

How common is CDAN1 p.Pro672= (c.2016G>A) in the general population?

CDAN1 p.Pro672= (c.2016G>A) is ultra-rare (popmax 0.0291%, nfe) (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.Pro672=

c.2016G>A · rs371799686 · VCV315939

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0291%, nfe)

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 -14	GERP -4
Overall
CADD	0.304	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0291% European (non-Finnish) · 343/1,179,014 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0255%

Overall 0.0234% 378/1,612,032 alleles · ultra-rare exomes 346/1,459,676 · genomes 32/152,356 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0291%	3,437
African / African-American	0.0227%	4,412
Admixed American	0.0151%	6,633
Remaining individualsnot grpmax-eligible	0.00641%	15,606
South Asian	0.00551%	18,165

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.Pro672=
Coding: c.2016G>A
MANE Select: NM_138477
dbSNP: rs371799686
Type: single nucleotide variant
Location: chr15:42730756 (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 672: a UniProt-annotated variant site (in cdan1a)

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.Pro672Leu Pathogenic/Likely pathogenic ★★ ⚠ 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-pro672 (accessed [today's date]).

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