Is MFSD8 p.Pro375fs (c.1124del) pathogenic?

MFSD8 p.Pro375fs (c.1124del) is classified Pathogenic/Likely pathogenic in MFSD8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-04-25). No gnomAD frequency available for this variant; Associated with neuronal ceroid lipofuscinosis 7.

What condition is associated with MFSD8 p.Pro375fs (c.1124del)?

MFSD8 p.Pro375fs (c.1124del) is associated with neuronal ceroid lipofuscinosis 7, macular dystrophy with central cone involvement (ClinVar).

How common is MFSD8 p.Pro375fs (c.1124del) in the general population?

MFSD8 p.Pro375fs (c.1124del) is no gnomAD frequency available for this variant (gnomAD).

MFSD8 p.Pro375fs

c.1124del · rs1578794927 · VCV802088

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neuronal ceroid lipofuscinosis 7

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 11 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP -5, 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: MFSD8
Protein: p.Pro375fs
Coding: c.1124del
MANE Select: NM_001371596
dbSNP: rs1578794927
Type: Deletion
Location: chr4:127921750 (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

neuronal ceroid lipofuscinosis 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: macular dystrophy with central cone involvement

For CLN7 disease (Orphanet):

Onset: Infancy

Similar variants

MFSD8 c.1103-2del Likely pathogenic ★★ same condition
MFSD8 p.Gly179fs Pathogenic/Likely pathogenic ★★ same condition
MFSD8 p.Gly197fs Pathogenic/Likely pathogenic ★★ same condition
MFSD8 p.Gly446fs Pathogenic/Likely pathogenic ★★ same condition
MFSD8 p.Phe471fs Pathogenic/Likely pathogenic ★★ same condition
MFSD8 p.Trp387fs Pathogenic/Likely pathogenic ★★ same condition
MFSD8 p.Val327fs Pathogenic ★★ same condition
MFSD8 p.Val346fs Pathogenic/Likely 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-pro375fs (accessed [today's date]).

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