Is CDAN1 p.Thr656= (c.1968C>T) pathogenic?

CDAN1 p.Thr656= (c.1968C>T) is classified Benign in CDAN1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Low-frequency (popmax 3.76%, afr); Associated with congenital dyserythropoietic anemia type 1.

What condition is associated with CDAN1 p.Thr656= (c.1968C>T)?

CDAN1 p.Thr656= (c.1968C>T) is associated with congenital dyserythropoietic anemia type 1, anemia, congenital dyserythropoietic, type 1a (ClinVar).

How common is CDAN1 p.Thr656= (c.1968C>T) in the general population?

CDAN1 p.Thr656= (c.1968C>T) is low-frequency (popmax 3.76%, afr) (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.Thr656=

c.1968C>T · rs61742992 · VCV315942

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.76%, afr)

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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.75 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.042	GERP -4, phastCons 0.51
Overall
CADD	8.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.76% African / African-American · 2,824/75,042 alleles

Filtering AF 3.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.6%

Overall 0.211% 3,408/1,614,166 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.76%	27
Middle Eastern	0.528%	189
Remaining individualsnot grpmax-eligible	0.323%	309
Admixed American	0.267%	375
Ashkenazi Jewishnot grpmax-eligible	0.193%	519
South Asian	0.0285%	3,503
European (non-Finnish)	0.00898%	11,132
East Asian	0.00223%	44,868

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.Thr656=
Coding: c.1968C>T
MANE Select: NM_138477
dbSNP: rs61742992
Type: single nucleotide variant
Location: chr15:42730964 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.58 · 2 PDB

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.Thr656Ser Likely benign ★★ same residue
CDAN1 p.Thr656Ile 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-thr656 (accessed [today's date]).

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