Is FIG4 p.Ser730fs (c.2188dup) pathogenic?

FIG4 p.Ser730fs (c.2188dup) is classified Pathogenic in FIG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-23). No gnomAD frequency available for this variant.

How common is FIG4 p.Ser730fs (c.2188dup) in the general population?

FIG4 p.Ser730fs (c.2188dup) is no gnomAD frequency available for this variant (gnomAD).

FIG4 p.Ser730fs

c.2188dup · rs1778129968 · VCV987031

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

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 20 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.6	GERP -0.45, 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: FIG4
Protein: p.Ser730fs
Coding: c.2188dup
MANE Select: NM_014845
dbSNP: rs1778129968
Type: Duplication
Location: chr6:109791379 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.65 · 1 PDB
Residue 730: the 'disordered' region

Full FIG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FIG4 p.Glu767fs Pathogenic/Likely pathogenic ★★ same type
FIG4 p.Leu458fs Pathogenic ★★ same type
FIG4 p.Pro605fs Pathogenic ★★ same type
FIG4 p.Ser750fs Pathogenic ★★ same type
FIG4 p.Thr556fs Pathogenic/Likely pathogenic ★★ same type
FIG4 p.Thr689fs Pathogenic/Likely pathogenic ★★ same type
FIG4 p.Gln888fs Uncertain significance ★★ same type
FIG4 c.1889+6_1889+11dup 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/fig4-p-ser730fs (accessed [today's date]).

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