Is CDIN1 p.Ala100Ser (c.298G>T) pathogenic?

CDIN1 p.Ala100Ser (c.298G>T) is classified Uncertain significance in CDIN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-17). AlphaMissense: likely benign (0.2547); Ultra-rare (popmax 0.0133%, nfe); Associated with congenital dyserythropoietic anemia type type 1B.

What condition is associated with CDIN1 p.Ala100Ser (c.298G>T)?

CDIN1 p.Ala100Ser (c.298G>T) is associated with congenital dyserythropoietic anemia type type 1B (ClinVar).

How common is CDIN1 p.Ala100Ser (c.298G>T) in the general population?

CDIN1 p.Ala100Ser (c.298G>T) is ultra-rare (popmax 0.0133%, nfe) (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.Ala100Ser (c.298G>T)?

AlphaMissense predicts likely benign (score 0.2547) — an in-silico prediction, not a clinical call.

CDIN1 p.Ala100Ser

c.298G>T · rs201022722 · VCV2688694

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2547 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital dyserythropoietic anemia type type 1B

Computational evidence

Protein change
AlphaMissense	0.2547	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -8.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 229 kb · p 0.048 · regional, not allelic
Overall
CADD	24.6	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 0.0133% European (non-Finnish) · 157/1,178,942 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.0102% 164/1,611,650 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0133%	7,509
Remaining individualsnot grpmax-eligible	0.00481%	20,779
African / African-American	0.00267%	37,407
Admixed American	0.00167%	59,830
Finnishnot grpmax-eligible	0.00157%	63,818

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: CDIN1
Protein: p.Ala100Ser
Coding: c.298G>T
MANE Select: NM_001321759
dbSNP: rs201022722
Type: single nucleotide variant
Location: chr15:36657857 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.59

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.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
CDIN1 c.274-82T>A 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-ala100ser (accessed [today's date]).

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