Is CDIN1 p.Leu73Val (c.217C>G) pathogenic?

CDIN1 p.Leu73Val (c.217C>G) is classified Benign/Likely benign in CDIN1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0758); Common (popmax 67.2%, eas) — too common for a highly-penetrant pathogenic allele; Associated with congenital dyserythropoietic anemia type type 1B.

What condition is associated with CDIN1 p.Leu73Val (c.217C>G)?

CDIN1 p.Leu73Val (c.217C>G) is associated with congenital dyserythropoietic anemia type type 1B (ClinVar).

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.Leu73Val (c.217C>G)?

AlphaMissense predicts likely benign (score 0.0758) — an in-silico prediction, not a clinical call.

CDIN1 p.Leu73Val

Q: How common is CDIN1 p.Leu73Val (c.217C>G) in the general population?

CDIN1 p.Leu73Val (c.217C>G) is common (popmax 67.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.217C>G · rs3784678 · VCV257532

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0758 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 67.2%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital dyserythropoietic anemia type type 1B

Computational evidence

Protein change
AlphaMissense	0.0758	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -6.97	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 3.4	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 229 kb · p 0.048 · regional, not allelic
Overall
CADD	23.3	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 67.2% East Asian · 29,249/43,546 alleles

Filtering AF 66.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 66.3%

Overall 47.2% 742,330/1,573,246 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	67.2%	1
South Asian	59%	2
Amishnot grpmax-eligible	56.2%	2
Middle Eastern	47.5%	2
European (non-Finnish)	46.9%	2
Remaining individualsnot grpmax-eligible	46.8%	2
Ashkenazi Jewishnot grpmax-eligible	44%	2
Finnishnot grpmax-eligible	43.5%	2
African / African-American	39.4%	3
Admixed American	35.3%	3

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.Leu73Val
Coding: c.217C>G
MANE Select: NM_001321759
dbSNP: rs3784678
Type: single nucleotide variant
Location: chr15:36654102 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.59
Residue 73: a UniProt-annotated variant site (in)

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-leu73val (accessed [today's date]).

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