Is SEC23B p.Ile501= (c.1503C>T) pathogenic?

SEC23B p.Ile501= (c.1503C>T) is classified Benign/Likely benign in SEC23B (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-27). Low-frequency (popmax 2.14%, afr); Associated with congenital dyserythropoietic anemia type 2.

What condition is associated with SEC23B p.Ile501= (c.1503C>T)?

SEC23B p.Ile501= (c.1503C>T) is associated with congenital dyserythropoietic anemia type 2, Cowden syndrome 7 (ClinVar).

How common is SEC23B p.Ile501= (c.1503C>T) in the general population?

SEC23B p.Ile501= (c.1503C>T) is low-frequency (popmax 2.14%, afr) (gnomAD).

How is Congenital dyserythropoietic anemia type II inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SEC23B p.Ile501=

c.1503C>T · rs147036760 · VCV95383

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.14%, afr)

Conditions

congenital dyserythropoietic anemia type 2

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 · C>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.099	GERP -5.4, phastCons 0.82
Overall
CADD	9.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.14% African / African-American · 1,609/75,062 alleles

Filtering AF 2.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.02%

Overall 0.121% 1,949/1,614,036 alleles · low-frequency exomes 982/1,461,680 · genomes 967/152,356 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.14%	47
Middle Eastern	0.858%	117
Remaining individualsnot grpmax-eligible	0.171%	584
Admixed American	0.15%	667
East Asian	0.0267%	3,740
European (non-Finnish)	0.00644%	15,524
South Asian	0.00329%	30,363

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: SEC23B
Protein: p.Ile501=
Coding: c.1503C>T
MANE Select: NM_006363
dbSNP: rs147036760
Type: single nucleotide variant
Location: chr20:18542394 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.41

Full SEC23B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital dyserythropoietic anemia type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Cowden syndrome 7

For Congenital dyserythropoietic anemia type II (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

SEC23B c.1314+1G>A Likely pathogenic ★★ same condition
SEC23B c.835-2A>G Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.Ala524Val Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.Arg14Trp Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.Arg264Ter Pathogenic ★★ same condition
SEC23B p.Arg313His Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.Arg324Ter Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.Arg339Ter 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/sec23b-p-ile501 (accessed [today's date]).

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