Is MFSD8 p.Gly343= (c.1029A>G) pathogenic?

MFSD8 p.Gly343= (c.1029A>G) is classified Likely benign in MFSD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). Very rare (popmax 0.00333%, amr); Associated with neuronal ceroid lipofuscinosis 7.

What condition is associated with MFSD8 p.Gly343= (c.1029A>G)?

MFSD8 p.Gly343= (c.1029A>G) is associated with neuronal ceroid lipofuscinosis 7 (ClinVar).

How common is MFSD8 p.Gly343= (c.1029A>G) in the general population?

MFSD8 p.Gly343= (c.1029A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

MFSD8 p.Gly343=

c.1029A>G · rs1220404877 · VCV1586629

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

neuronal ceroid lipofuscinosis 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	acceptor loss · deltas
Pangolin	Δ0.23	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.67	GERP -4.2, phastCons 1
Overall
CADD	9.424	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,986 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,952 alleles · very rare exomes 2/1,461,842 · genomes 0/152,110 · 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.Gly343=
Coding: c.1029A>G
MANE Select: NM_001371596
dbSNP: rs1220404877
Type: single nucleotide variant
Location: chr4:127921933 (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-gly343 (accessed [today's date]).

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