Is SEC23B p.Asp756= (c.2268C>T) pathogenic?

SEC23B p.Asp756= (c.2268C>T) is classified Conflicting classifications of pathogenicity in SEC23B (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-10-23). Rare (popmax 0.156%, sas); Associated with Cowden syndrome 7.

What condition is associated with SEC23B p.Asp756= (c.2268C>T)?

SEC23B p.Asp756= (c.2268C>T) is associated with Cowden syndrome 7, congenital dyserythropoietic anemia type 2 (ClinVar).

How common is SEC23B p.Asp756= (c.2268C>T) in the general population?

SEC23B p.Asp756= (c.2268C>T) is rare (popmax 0.156%, sas) (gnomAD).

SEC23B p.Asp756=

c.2268C>T · rs530834583 · VCV1163743

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.156%, sas)

Conditions

Cowden syndrome 7

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 0.76	GERP -5.1, phastCons 1
Overall
CADD	4.453	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.156% South Asian · 142/91,080 alleles

Filtering AF 0.135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.127%

Overall 0.00954% 154/1,614,076 alleles · rare exomes 141/1,461,814 · genomes 13/152,262 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.156%	641
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0096%	10,418
African / African-American	0.00133%	75,024
European (non-Finnish)	0.000339%	294,989

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.Asp756=
Coding: c.2268C>T
MANE Select: NM_006363
dbSNP: rs530834583
Type: single nucleotide variant
Location: chr20:18560704 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.41
Residue 756: a UniProt-annotated variant site (in cdan2)

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

Disease context

Cowden syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital dyserythropoietic anemia type 2

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-asp756 (accessed [today's date]).

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