Is CDIN1 p.Pro20Arg (c.59C>G) pathogenic?

CDIN1 p.Pro20Arg (c.59C>G) is classified Uncertain significance in CDIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-11). AlphaMissense: ambiguous (0.42); Absent from gnomAD v4.1; Associated with congenital dyserythropoietic anemia type type 1B.

What condition is associated with CDIN1 p.Pro20Arg (c.59C>G)?

CDIN1 p.Pro20Arg (c.59C>G) is associated with congenital dyserythropoietic anemia type type 1B (ClinVar).

How common is CDIN1 p.Pro20Arg (c.59C>G) in the general population?

CDIN1 p.Pro20Arg (c.59C>G) is absent from gnomAD v4.1 (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 CDIN1 p.Pro20Arg (c.59C>G)?

AlphaMissense predicts ambiguous (score 0.42) — an in-silico prediction, not a clinical call.

CDIN1 p.Pro20Arg

c.59C>G · rs1595696464 · VCV692133

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.42 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

congenital dyserythropoietic anemia type type 1B

Computational evidence

Protein change
AlphaMissense	0.42	ambiguous
REVEL	0.126	moderately benign-leaning
SaProt	LLR -3.53	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 229 kb · p 0.048 · regional, not allelic
Overall
CADD	27.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDIN1
Protein: p.Pro20Arg
Coding: c.59C>G
MANE Select: NM_001321759
dbSNP: rs1595696464
Type: single nucleotide variant
Location: chr15:36579919 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.59
Residue 20: a UniProt-annotated variant site (in cdan1b; uncertain significance)

Full CDIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital dyserythropoietic anemia type type 1B — 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

CDIN1 p.Ala100Ser Uncertain significance ★★ ⚠ same condition
CDIN1 p.Arg101Trp Uncertain significance ★★ ⚠ same condition
CDIN1 p.Glu66Ala Uncertain significance ★★ ⚠ same condition
CDIN1 p.Pro33Leu Uncertain significance ★★ ⚠ same condition
CDIN1 p.Thr271Lys Uncertain significance ★★ ⚠ same condition
CDIN1 p.Tyr236Cys Uncertain significance ★★ ⚠ same condition
CDIN1 c.148-19G>T Benign/Likely benign ★★ same condition
CDIN1 c.273+82C>T Benign ★★ 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/cdin1-p-pro20arg (accessed [today's date]).

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