Is SEC23B p.Phe463fs (c.1389_1390del) pathogenic?

SEC23B p.Phe463fs (c.13891390del) is classified Pathogenic in SEC23B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). Very rare (popmax 0.00267%, afr); Associated with Cowden syndrome 7.

What condition is associated with SEC23B p.Phe463fs (c.1389_1390del)?

SEC23B p.Phe463fs (c.1389_1390del) is associated with Cowden syndrome 7, congenital dyserythropoietic anemia type 2 (ClinVar).

How common is SEC23B p.Phe463fs (c.1389_1390del) in the general population?

SEC23B p.Phe463fs (c.1389_1390del) is very rare (popmax 0.00267%, afr) (gnomAD).

SEC23B p.Phe463fs

c.1389_1390del · VCV3753233

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Cowden syndrome 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Overall
CADD	36.0	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 0.00267% African / African-American · 2/74,940 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000682% 11/1,613,726 alleles · very rare exomes 9/1,461,502 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,470
European (non-Finnish)	0.000763%	131,079

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.Phe463fs
Coding: c.1389_1390del
MANE Select: NM_006363
Type: Deletion
Location: chr20:18535727 (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 c.1511+2_1511+5del Likely pathogenic ★★ same condition
SEC23B p.Ala717fs Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.Arg554fs Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.Glu415fs Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.His631fs Pathogenic/Likely pathogenic ★★ same condition
SEC23B c.1404+20_1404+21del Benign ★★ same condition
SEC23B c.1314_1314+10del Likely pathogenic ★ same condition
SEC23B p.Arg611fs 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-phe463fs (accessed [today's date]).

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