Is INF2 p.Ser1237fs (c.3709del) pathogenic?

INF2 p.Ser1237fs (c.3709del) is classified Uncertain significance in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-28). No gnomAD frequency available for this variant; Associated with Charcot-Marie-Tooth disease dominant intermediate E.

How common is INF2 p.Ser1237fs (c.3709del) in the general population?

INF2 p.Ser1237fs (c.3709del) is no gnomAD frequency available for this variant (gnomAD).

INF2 p.Ser1237fs

Q: What condition is associated with INF2 p.Ser1237fs (c.3709del)?

INF2 p.Ser1237fs (c.3709del) is associated with Charcot-Marie-Tooth disease dominant intermediate E, focal segmental glomerulosclerosis 5 (ClinVar).

Q: How is Autosomal dominant intermediate Charcot-Marie-Tooth disease type E inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

c.3709del · rs2541955759 · VCV2951348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Charcot-Marie-Tooth disease dominant intermediate E

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (22 of 23, 43 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP 5.2, phastCons 0.94

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: INF2
Protein: p.Ser1237fs
Coding: c.3709del
MANE Select: NM_022489
dbSNP: rs2541955759
Type: Deletion
Location: chr14:104715297 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 1237: the 'disordered' region

Full INF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease dominant intermediate E — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: focal segmental glomerulosclerosis 5

For Autosomal dominant intermediate Charcot-Marie-Tooth disease type E (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: No data available

Similar variants

INF2 p.Ser1237Thr Likely benign ★ same residue
INF2 p.Ala164_Asp166del Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Leu406_Ser409del Uncertain significance ★★ same condition
INF2 p.Lys1243fs Uncertain significance ★★ same condition
INF2 p.Pro459_Pro462del Uncertain significance ★★ same condition
INF2 p.Ser1215fs Uncertain significance ★★ same condition
INF2 p.Thr1242fs Uncertain significance ★★ same condition
INF2 c.2310+12del 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/inf2-p-ser1237fs (accessed [today's date]).

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