Is MFSD8 p.Pro292= (c.876A>G) pathogenic?

MFSD8 p.Pro292= (c.876A>G) is classified Likely benign in MFSD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-01). Very rare (popmax 0.00134%, afr); Associated with neuronal ceroid lipofuscinosis 7.

What condition is associated with MFSD8 p.Pro292= (c.876A>G)?

MFSD8 p.Pro292= (c.876A>G) is associated with neuronal ceroid lipofuscinosis 7 (ClinVar).

How common is MFSD8 p.Pro292= (c.876A>G) in the general population?

MFSD8 p.Pro292= (c.876A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

MFSD8 p.Pro292=

c.876A>G · rs770483205 · VCV1585463

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 -5.4	GERP -4.6
Overall
CADD	6.989	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,806 alleles

Overall 0.000186% 3/1,610,584 alleles · very rare exomes 2/1,458,506 · genomes 1/152,078 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,806
South Asian	0.00111%	89,736
European (non-Finnish)	8.48e-05%	1,178,743

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.Pro292=
Coding: c.876A>G
MANE Select: NM_001371596
dbSNP: rs770483205
Type: single nucleotide variant
Location: chr4:127930805 (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 p.Pro292_Leu293insTer Pathogenic ★ same residue
MFSD8 p.Pro292Ser Uncertain significance ★ ⚠ same residue
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

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-pro292 (accessed [today's date]).

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