Is CDAN1 p.Pro268Arg (c.803C>G) pathogenic?

CDAN1 p.Pro268Arg (c.803C>G) is classified Uncertain significance in CDAN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-10). AlphaMissense: likely benign (0.0859); Ultra-rare (popmax 0.0174%, afr); Associated with anemia, congenital dyserythropoietic, type 1a.

What condition is associated with CDAN1 p.Pro268Arg (c.803C>G)?

CDAN1 p.Pro268Arg (c.803C>G) is associated with anemia, congenital dyserythropoietic, type 1a (ClinVar).

How common is CDAN1 p.Pro268Arg (c.803C>G) in the general population?

CDAN1 p.Pro268Arg (c.803C>G) is ultra-rare (popmax 0.0174%, afr) (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.Pro268Arg (c.803C>G)?

AlphaMissense predicts likely benign (score 0.0859) — an in-silico prediction, not a clinical call.

CDAN1 p.Pro268Arg

c.803C>G · rs151004903 · VCV2439834

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0859 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

anemia, congenital dyserythropoietic, type 1a

Computational evidence

Protein change
AlphaMissense	0.0859	likely benign
REVEL	0.381	indeterminate
SaProt	LLR -7.71	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 5.1	GERP 1.2, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,562 bp · p 0.0016 · regional, not allelic
Overall
CADD	21.7	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 0.0174% African / African-American · 13/74,898 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00229% 37/1,613,980 alleles · ultra-rare exomes 28/1,461,826 · genomes 9/152,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,761
European (non-Finnish)	0.00195%	51,305
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Pro268Arg
Coding: c.803C>G
MANE Select: NM_138477
dbSNP: rs151004903
Type: single nucleotide variant
Location: chr15:42735650 (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.Pro268= Benign/Likely benign ★★ 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-pro268arg (accessed [today's date]).

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