Is MFSD8 p.Val488= (c.1464G>A) pathogenic?

MFSD8 p.Val488= (c.1464G>A) is classified Uncertain significance in MFSD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-23). Very rare (popmax 0.00223%, eas); Associated with neuronal ceroid lipofuscinosis 7.

What condition is associated with MFSD8 p.Val488= (c.1464G>A)?

MFSD8 p.Val488= (c.1464G>A) is associated with neuronal ceroid lipofuscinosis 7 (ClinVar).

How common is MFSD8 p.Val488= (c.1464G>A) in the general population?

MFSD8 p.Val488= (c.1464G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

MFSD8 p.Val488=

c.1464G>A · VCV3721375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

neuronal ceroid lipofuscinosis 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.66	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -0.7	GERP -2.9, phastCons 0.008
Overall
CADD	5.706	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,874 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,074 alleles · very rare exomes 3/1,461,862 · genomes 0/152,212 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
European (non-Finnish)	0.000169%	590,002

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MFSD8
Protein: p.Val488=
Coding: c.1464G>A
MANE Select: NM_001371596
Type: single nucleotide variant
Location: chr4:127920723 (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

For CLN7 disease (Orphanet):

Onset: Infancy

Similar variants

MFSD8 c.1102+1G>A Likely pathogenic ★★ same condition
MFSD8 c.1102+2T>C Pathogenic/Likely pathogenic ★★ same condition
MFSD8 c.1350+2T>C Pathogenic/Likely pathogenic ★★ same condition
MFSD8 c.154+1G>A Likely pathogenic ★★ same condition
MFSD8 c.198+2T>C Pathogenic/Likely pathogenic ★★ same condition
MFSD8 c.439+2T>A Likely pathogenic ★★ same condition
MFSD8 c.440-2A>T Likely pathogenic ★★ same condition
MFSD8 c.553+1G>A 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-val488 (accessed [today's date]).

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