Is MFSD8 p.Pro18= (c.54T>G) pathogenic?

MFSD8 p.Pro18= (c.54T>G) is classified Likely benign in MFSD8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-09). Ultra-rare (popmax 0.0167%, amr); Associated with Inborn genetic diseases.

What condition is associated with MFSD8 p.Pro18= (c.54T>G)?

MFSD8 p.Pro18= (c.54T>G) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis 7, late infantile neuronal ceroid lipofuscinosis (ClinVar).

How common is MFSD8 p.Pro18= (c.54T>G) in the general population?

MFSD8 p.Pro18= (c.54T>G) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

MFSD8 p.Pro18=

c.54T>G · rs1243416801 · VCV700519

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Conditions

Inborn genetic diseases

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 0.19	GERP -2.9, phastCons 0.95
Overall
CADD	8.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/59,972 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00682%

Overall 0.00062% 10/1,613,720 alleles · ultra-rare exomes 8/1,461,460 · genomes 2/152,260 · 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.Pro18=
Coding: c.54T>G
MANE Select: NM_001371596
dbSNP: rs1243416801
Type: single nucleotide variant
Location: chr4:127965080 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.20
Residue 18: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuronal ceroid lipofuscinosis 7 late infantile neuronal ceroid lipofuscinosis

Similar variants

MFSD8 p.Pro18Ser 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
MFSD8 c.440-2A>T 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-pro18 (accessed [today's date]).

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