Is PIGN p.Ser702fs (c.2102dup) pathogenic?

PIGN p.Ser702fs (c.2102dup) is classified Pathogenic in PIGN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). Associated with multiple congenital anomalies-hypotonia-seizures syndrome 1.

What condition is associated with PIGN p.Ser702fs (c.2102dup)?

PIGN p.Ser702fs (c.2102dup) is associated with multiple congenital anomalies-hypotonia-seizures syndrome 1 (ClinVar).

PIGN p.Ser702fs

c.2102dup · VCV3655145

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

multiple congenital anomalies-hypotonia-seizures syndrome 1

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 23 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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

Variant & gene context

Gene: PIGN
Protein: p.Ser702fs
Coding: c.2102dup
MANE Select: NM_176787
Type: Duplication
Location: chr18:62095925 (GRCh38)
Gene constraint: LOEUF 1.46 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.33

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

Disease context

multiple congenital anomalies-hypotonia-seizures syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIGN p.Ala273fs Pathogenic/Likely pathogenic ★★ same condition
PIGN p.Gly800fs Pathogenic ★★ same condition
PIGN p.Leu499fs Pathogenic/Likely pathogenic ★★ same condition
PIGN p.Met328fs Pathogenic/Likely pathogenic ★★ same condition
PIGN c.1116+12dup Benign/Likely benign ★★ same condition
PIGN c.2577-13dup Benign/Likely benign ★★ same condition
PIGN c.2620-17_2620-15dup Likely benign ★★ same condition
PIGN c.2620-17_2620-16dup Benign/Likely benign ★★ 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/pign-p-ser702fs (accessed [today's date]).

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