Is SEC63 p.Asp609fs (c.1824_1825insTC) pathogenic?

SEC63 p.Asp609fs (c.18241825insTC) is classified Likely pathogenic in SEC63 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-02-06). No gnomAD frequency available for this variant; Associated with SEC63-related disorder.

What condition is associated with SEC63 p.Asp609fs (c.1824_1825insTC)?

SEC63 p.Asp609fs (c.1824_1825insTC) is associated with SEC63-related disorder (ClinVar).

How common is SEC63 p.Asp609fs (c.1824_1825insTC) in the general population?

SEC63 p.Asp609fs (c.1824_1825insTC) is no gnomAD frequency available for this variant (gnomAD).

SEC63 p.Asp609fs

c.1824_1825insTC · rs2481999708 · VCV3061377

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

SEC63-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 17 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SEC63
Protein: p.Asp609fs
Coding: c.1824_1825insTC
MANE Select: NM_007214
dbSNP: rs2481999708
Type: Insertion
Location: chr6:107882996 (GRCh38)
Gene constraint: LOEUF 0.532 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.71
Residue 609: the 'disordered' region; a UniProt-annotated variant site (in pcld2)

Full SEC63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SEC63-related disorder

Similar variants

SEC63 c.340-3_340-2insCCT Likely benign same condition
SEC63 p.Arg239Ter Pathogenic/Likely pathogenic ★★ same condition
SEC63 p.Arg98Ter Pathogenic/Likely pathogenic ★★ same condition
SEC63 p.His669fs Pathogenic/Likely pathogenic ★★ same condition
SEC63 p.Ser632Ter Pathogenic/Likely pathogenic ★★ same condition
SEC63 c.224+1G>C Likely pathogenic ★ same condition
SEC63 c.829-2A>G Likely pathogenic ★ same condition
SEC63 p.Arg45Ter 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/sec63-p-asp609fs (accessed [today's date]).

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