Is SEC63 p.Glu352fs (c.1052_1053insGGTGGAAATAT) pathogenic?

SEC63 p.Glu352fs (c.10521053insGGTGGAAATAT) is classified Pathogenic in SEC63 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-15). Very rare (popmax 8.54e-05%, nfe).

How common is SEC63 p.Glu352fs (c.1052_1053insGGTGGAAATAT) in the general population?

SEC63 p.Glu352fs (c.1052_1053insGGTGGAAATAT) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

SEC63 p.Glu352fs

c.1052_1053insGGTGGAAATAT · rs2482064962 · VCV1945120

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

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 11 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.54e-05% European (non-Finnish) · 1/1,170,806 alleles

Overall 6.23e-05% 1/1,604,074 alleles · very rare exomes 1/1,451,758 · genomes 0/152,316 · joint denominator

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: SEC63
Protein: p.Glu352fs
Coding: c.1052_1053insGGTGGAAATAT
MANE Select: NM_007214
dbSNP: rs2482064962
Type: Insertion
Location: chr6:107904630 (GRCh38)
Gene constraint: LOEUF 0.532 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.71
Residue 352: 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

Similar variants

SEC63 c.340-13_340-12insCCC Benign ★★ same type
SEC63 c.340-13_340-12insCCCC Benign ★★ same type
SEC63 p.Asn582fs Likely pathogenic ★ same type
SEC63 p.Pro542_Gln543insThr Conflicting classifications of pathogenicity ★ same type
SEC63 p.Tyr692fs Uncertain significance ★ same type
SEC63 c.1936-11_1936-10insTG Likely benign ★ same type
SEC63 c.1936-12_1936-11insG Likely benign ★ same type
SEC63 c.340-13_340-12insCCCCC Likely benign ★ same type

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-glu352fs (accessed [today's date]).

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