Is SEC23B p.Ser603= (c.1809A>G) pathogenic?

SEC23B p.Ser603= (c.1809A>G) is classified Conflicting classifications of pathogenicity in SEC23B (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-08). Rare (popmax 0.693%, mid); Associated with congenital dyserythropoietic anemia type 2.

What condition is associated with SEC23B p.Ser603= (c.1809A>G)?

SEC23B p.Ser603= (c.1809A>G) is associated with congenital dyserythropoietic anemia type 2, Cowden syndrome 7 (ClinVar).

How common is SEC23B p.Ser603= (c.1809A>G) in the general population?

SEC23B p.Ser603= (c.1809A>G) is rare (popmax 0.693%, mid) (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.Ser603=

c.1809A>G · rs139882548 · VCV337798

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.693%, mid)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -5.7
Overall
CADD	0.334	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.693% Middle Eastern · 42/6,062 alleles

Filtering AF 0.527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.469%

Overall 0.0344% 556/1,614,094 alleles · rare exomes 518/1,461,808 · genomes 38/152,286 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.693%	144
South Asian	0.165%	607
Remaining individualsnot grpmax-eligible	0.0976%	1,025
African / African-American	0.032%	3,127
East Asian	0.0223%	4,488
European (non-Finnish)	0.0216%	4,627
Admixed American	0.02%	5,002
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803

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.Ser603=
Coding: c.1809A>G
MANE Select: NM_006363
dbSNP: rs139882548
Type: single nucleotide variant
Location: chr20:18548674 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.41
Residue 603: a UniProt-annotated variant site (in cdan2)

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-ser603 (accessed [today's date]).

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