Is MFSD8 p.Pro62= (c.186A>T) pathogenic?

MFSD8 p.Pro62= (c.186A>T) is classified Likely benign in MFSD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-29). Very rare (popmax 0.000339%, nfe); Associated with neuronal ceroid lipofuscinosis 7.

What condition is associated with MFSD8 p.Pro62= (c.186A>T)?

MFSD8 p.Pro62= (c.186A>T) is associated with neuronal ceroid lipofuscinosis 7 (ClinVar).

How common is MFSD8 p.Pro62= (c.186A>T) in the general population?

MFSD8 p.Pro62= (c.186A>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

MFSD8 p.Pro62=

c.186A>T · rs750969105 · VCV1569141

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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
Constraint at this position
Conservation	phyloP -2.5	GERP -3.5
Overall
CADD	7.697	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,016 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,612,222 alleles · very rare exomes 4/1,459,884 · genomes 0/152,338 · joint denominator

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.Pro62=
Coding: c.186A>T
MANE Select: NM_001371596
dbSNP: rs750969105
Type: single nucleotide variant
Location: chr4:127949816 (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-pro62 (accessed [today's date]).

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