Is CDIN1 p.Arg101Trp (c.301C>T) pathogenic?

CDIN1 p.Arg101Trp (c.301C>T) is classified Uncertain significance in CDIN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-17). AlphaMissense: likely pathogenic (0.8498); Very rare (popmax 0.00941%, nfe); Associated with congenital dyserythropoietic anemia type type 1B.

What condition is associated with CDIN1 p.Arg101Trp (c.301C>T)?

CDIN1 p.Arg101Trp (c.301C>T) is associated with congenital dyserythropoietic anemia type type 1B (ClinVar).

How common is CDIN1 p.Arg101Trp (c.301C>T) in the general population?

CDIN1 p.Arg101Trp (c.301C>T) is very rare (popmax 0.00941%, 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.Arg101Trp (c.301C>T)?

AlphaMissense predicts likely pathogenic (score 0.8498) — an in-silico prediction, not a clinical call.

CDIN1 p.Arg101Trp

c.301C>T · VCV3712634

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00941%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital dyserythropoietic anemia type type 1B

Computational evidence

Protein change
AlphaMissense	0.8498	likely pathogenic
REVEL	0.486	indeterminate
SaProt	LLR -12.25	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 229 kb · p 0.048 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00941% European (non-Finnish) · 111/1,179,006 alleles

Filtering AF 0.00792% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00744%

Overall 0.00751% 121/1,611,824 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00963%	10,389
European (non-Finnish)grpmax	0.00941%	10,622
African / African-American	0.00401%	24,937
South Asian	0.0011%	90,626

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg101Trp
Coding: c.301C>T
MANE Select: NM_001321759
Type: single nucleotide variant
Location: chr15:36657860 (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.Ala100Ser 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-arg101trp (accessed [today's date]).

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