Is CDAN1 p.Pro86Ser (c.256C>T) pathogenic?

CDAN1 p.Pro86Ser (c.256C>T) is classified Conflicting classifications of pathogenicity in CDAN1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-30). AlphaMissense: likely benign (0.0693); Rare (popmax 0.509%, mid); Associated with congenital dyserythropoietic anemia type 1.

What condition is associated with CDAN1 p.Pro86Ser (c.256C>T)?

CDAN1 p.Pro86Ser (c.256C>T) is associated with congenital dyserythropoietic anemia type 1, anemia, congenital dyserythropoietic, type 1a (ClinVar).

How common is CDAN1 p.Pro86Ser (c.256C>T) in the general population?

CDAN1 p.Pro86Ser (c.256C>T) is rare (popmax 0.509%, mid) (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.Pro86Ser (c.256C>T)?

AlphaMissense predicts likely benign (score 0.0693) — an in-silico prediction, not a clinical call.

CDAN1 p.Pro86Ser

c.256C>T · rs543791953 · VCV315953

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0693 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.509%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital dyserythropoietic anemia type 1

Computational evidence

Protein change
AlphaMissense	0.0693	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.47	donor gain · deltas
Constraint at this position
Conservation	phyloP 1.4	GERP -3.2, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,562 bp · p 0.0016 · regional, not allelic
Overall
CADD	19.12	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.509% Middle Eastern · 28/5,500 alleles

Filtering AF 0.362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.312%

Overall 0.0292% 440/1,507,556 alleles · rare exomes 406/1,355,542 · genomes 34/152,014 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.509%	196
Ashkenazi Jewishnot grpmax-eligible	0.396%	252
Remaining individualsnot grpmax-eligible	0.0775%	1,291
South Asian	0.0387%	2,587
Finnishnot grpmax-eligible	0.0201%	4,976
Admixed American	0.0194%	5,154
European (non-Finnish)	0.0178%	5,619
African / African-American	0.0102%	9,845

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.Pro86Ser
Coding: c.256C>T
MANE Select: NM_138477
dbSNP: rs543791953
Type: single nucleotide variant
Location: chr15:42736615 (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 86: 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.Pro86Leu 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-pro86ser (accessed [today's date]).

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