Is SEC23B p.Arg264Ter (c.790C>T) pathogenic?

SEC23B p.Arg264Ter (c.790C>T) is classified Pathogenic in SEC23B (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-12). Very rare (popmax 0.00329%, sas); Associated with Cowden syndrome 7.

What condition is associated with SEC23B p.Arg264Ter (c.790C>T)?

SEC23B p.Arg264Ter (c.790C>T) is associated with Cowden syndrome 7, congenital dyserythropoietic anemia type 2 (ClinVar).

How common is SEC23B p.Arg264Ter (c.790C>T) in the general population?

SEC23B p.Arg264Ter (c.790C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

SEC23B p.Arg264Ter

c.790C>T · rs121918224 · VCV1225

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

Cowden syndrome 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.12, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,080 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00223% 36/1,614,030 alleles · very rare exomes 33/1,461,864 · genomes 3/152,166 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,360
European (non-Finnish)	0.00254%	39,334
East Asian	0.00223%	44,890
Admixed American	0.00167%	60,008
African / African-American	0.00133%	74,912

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.Arg264Ter
Coding: c.790C>T
MANE Select: NM_006363
dbSNP: rs121918224
Type: single nucleotide variant
Location: chr20:18525888 (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

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

Also linked: congenital dyserythropoietic anemia type 2

Similar variants

SEC23B p.Arg264Gln Uncertain significance ★ ⚠ same residue
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.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-arg264ter (accessed [today's date]).

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