Is SEC23A p.Pro44fs (c.129del) pathogenic?

SEC23A p.Pro44fs (c.129del) is classified Uncertain significance in SEC23A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-17). Associated with craniolenticulosutural dysplasia.

What condition is associated with SEC23A p.Pro44fs (c.129del)?

SEC23A p.Pro44fs (c.129del) is associated with craniolenticulosutural dysplasia (ClinVar).

SEC23A p.Pro44fs

c.129del · VCV4729181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

craniolenticulosutural dysplasia

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 2 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: SEC23A
Protein: p.Pro44fs
Coding: c.129del
MANE Select: NM_006364
Type: Deletion
Location: chr14:39095990 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.86 · 38 PDB

Full SEC23A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

craniolenticulosutural dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SEC23A p.Asp50_Pro52del Uncertain significance ★ same condition
SEC23A p.Asp754fs Uncertain significance ★ same condition
SEC23A p.Leu60fs Uncertain significance ★ same condition
SEC23A p.Pro565fs Uncertain significance ★ same condition
SEC23A p.Ala284Pro Uncertain significance ★★ ⚠ same condition
SEC23A p.Ala478Ser Uncertain significance ★★ ⚠ same condition
SEC23A p.Arg123Cys Uncertain significance ★★ ⚠ same condition
SEC23A p.Arg476His Uncertain significance ★★ ⚠ 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/sec23a-p-pro44fs (accessed [today's date]).

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