Is MFSD8 p.Arg337Pro (c.1010G>C) pathogenic?

MFSD8 p.Arg337Pro (c.1010G>C) is classified Uncertain significance in MFSD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: likely pathogenic (0.6638); Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis 7.

What condition is associated with MFSD8 p.Arg337Pro (c.1010G>C)?

MFSD8 p.Arg337Pro (c.1010G>C) is associated with neuronal ceroid lipofuscinosis 7 (ClinVar).

How common is MFSD8 p.Arg337Pro (c.1010G>C) in the general population?

MFSD8 p.Arg337Pro (c.1010G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MFSD8 p.Arg337Pro (c.1010G>C)?

AlphaMissense predicts likely pathogenic (score 0.6638) — an in-silico prediction, not a clinical call.

MFSD8 p.Arg337Pro

c.1010G>C · rs200386040 · VCV1041380

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6638 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis 7

Computational evidence

Protein change
AlphaMissense	0.6638	likely pathogenic
REVEL	0.835	moderately pathogenic-leaning
SaProt	LLR -9.70	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 44 kb · p 0.0019 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MFSD8
Protein: p.Arg337Pro
Coding: c.1010G>C
MANE Select: NM_001371596
dbSNP: rs200386040
Type: single nucleotide variant
Location: chr4:127921952 (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.Arg337Cys Uncertain significance ★★ ⚠ same residue
MFSD8 p.Arg337His 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-arg337pro (accessed [today's date]).

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