Is SEC23B p.Asp409= (c.1227C>T) pathogenic?

SEC23B p.Asp409= (c.1227C>T) is classified Likely benign in SEC23B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). Ultra-rare (popmax 0.0746%, amr); Associated with congenital dyserythropoietic anemia type 2.

What condition is associated with SEC23B p.Asp409= (c.1227C>T)?

SEC23B p.Asp409= (c.1227C>T) is associated with congenital dyserythropoietic anemia type 2, Cowden syndrome 7 (ClinVar).

How common is SEC23B p.Asp409= (c.1227C>T) in the general population?

SEC23B p.Asp409= (c.1227C>T) is ultra-rare (popmax 0.0746%, amr) (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.Asp409=

c.1227C>T · rs890679369 · VCV2922593

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0746%, amr)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP -4, phastCons 1
Overall
CADD	7.857	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0746% Admixed American · 44/59,000 alleles

Filtering AF 0.057% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0509%

Overall 0.00368% 59/1,601,450 alleles · ultra-rare exomes 21/1,451,886 · genomes 38/149,564 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0746%	1,341
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,456
Remaining individualsnot grpmax-eligible	0.00322%	31,009
African / African-American	0.00135%	73,926
South Asian	0.00112%	89,402
European (non-Finnish)	0.000852%	117,334

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.Asp409=
Coding: c.1227C>T
MANE Select: NM_006363
dbSNP: rs890679369
Type: single nucleotide variant
Location: chr20:18530797 (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-asp409 (accessed [today's date]).

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