Is SEC63 p.Met479fs (c.1434_1435del) pathogenic?

SEC63 p.Met479fs (c.14341435del) is classified Likely pathogenic in SEC63 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-02-16). No gnomAD frequency available for this variant; Associated with SEC63-related disorder.

What condition is associated with SEC63 p.Met479fs (c.1434_1435del)?

SEC63 p.Met479fs (c.1434_1435del) is associated with SEC63-related disorder, autosomal dominant polycystic liver disease (ClinVar).

How common is SEC63 p.Met479fs (c.1434_1435del) in the general population?

SEC63 p.Met479fs (c.1434_1435del) is no gnomAD frequency available for this variant (gnomAD).

SEC63 p.Met479fs

c.1434_1435del · rs2114434218 · VCV1255605

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

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 14 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	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.Met479fs
Coding: c.1434_1435del
MANE Select: NM_007214
dbSNP: rs2114434218
Type: Deletion
Location: chr6:107897654 (GRCh38)
Gene constraint: LOEUF 0.532 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.71
Residue 479: a UniProt-annotated variant site (in pcld2); the sec63 1 domain

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

Disease context

SEC63-related disorder

Also linked: autosomal dominant polycystic liver disease

Similar variants

SEC63 p.His669fs Pathogenic/Likely pathogenic ★★ same condition
SEC63 p.Lys402fs Likely pathogenic ★ same condition
SEC63 p.Gln322fs Pathogenic same condition
SEC63 p.Ile120fs Pathogenic same condition
SEC63 p.Met141fs Pathogenic same condition
SEC63 p.Ala373_Gln375del Uncertain significance same condition
SEC63 c.340-13_340-7del Benign same condition
SEC63 p.Arg239Ter Pathogenic/Likely 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-met479fs (accessed [today's date]).

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