Is PIGN p.Val815fs (c.2443_2450del) pathogenic?

PIGN p.Val815fs (c.24432450del) is classified Pathogenic in PIGN (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-23). No gnomAD frequency available for this variant; Associated with multiple congenital anomalies-hypotonia-seizures syndrome 1.

What condition is associated with PIGN p.Val815fs (c.2443_2450del)?

PIGN p.Val815fs (c.2443_2450del) is associated with multiple congenital anomalies-hypotonia-seizures syndrome 1 (ClinVar).

How common is PIGN p.Val815fs (c.2443_2450del) in the general population?

PIGN p.Val815fs (c.2443_2450del) is no gnomAD frequency available for this variant (gnomAD).

PIGN p.Val815fs

c.2443_2450del · rs2033602281 · VCV935812

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 27 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP -0.4, 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: PIGN
Protein: p.Val815fs
Coding: c.2443_2450del
MANE Select: NM_176787
dbSNP: rs2033602281
Type: Deletion
Location: chr18:62084583 (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.Val815Ala Uncertain significance ★ same residue
PIGN c.548_549+6del Pathogenic/Likely pathogenic ★★ same condition
PIGN c.806-4_808del Likely pathogenic ★★ same condition
PIGN p.Ile746fs Pathogenic/Likely pathogenic ★★ same condition
PIGN p.Leu420fs Pathogenic/Likely pathogenic ★★ same condition
PIGN p.Lys647fs Pathogenic ★★ same condition
PIGN c.1116+12del Benign/Likely benign ★★ same condition
PIGN c.2620-5del 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-val815fs (accessed [today's date]).

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