Is MFSD8 p.Ser462fs (c.1385dup) pathogenic?

MFSD8 p.Ser462fs (c.1385dup) is classified Likely pathogenic in MFSD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). Associated with late infantile neuronal ceroid lipofuscinosis.

What condition is associated with MFSD8 p.Ser462fs (c.1385dup)?

MFSD8 p.Ser462fs (c.1385dup) is associated with late infantile neuronal ceroid lipofuscinosis (ClinVar).

MFSD8 p.Ser462fs

c.1385dup · VCV4816894

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

late infantile neuronal ceroid lipofuscinosis

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 in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.007	GERP -1.8, phastCons 0.017

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

Variant & gene context

Gene: MFSD8
Protein: p.Ser462fs
Coding: c.1385dup
MANE Select: NM_001371596
Type: Duplication
Location: chr4:127920801 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.20

Full MFSD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

late infantile neuronal ceroid lipofuscinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MFSD8 p.Thr73fs Pathogenic ★★ same condition
MFSD8 c.1102+2T>C Pathogenic/Likely pathogenic ★★ same condition
MFSD8 c.439+2T>A Likely pathogenic ★★ same condition
MFSD8 c.63-1G>A Pathogenic ★★ same condition
MFSD8 c.63-2A>G Pathogenic/Likely pathogenic ★★ same condition
MFSD8 c.699-1G>C Likely pathogenic ★★ same condition
MFSD8 c.754+1G>A Pathogenic/Likely pathogenic ★★ same condition
MFSD8 c.754+1G>C Pathogenic ★★ 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/mfsd8-p-ser462fs (accessed [today's date]).

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