Is MN1 p.Val1283= (c.3849C>T) pathogenic?

MN1 p.Val1283= (c.3849C>T) is classified Likely benign in MN1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-19). Very rare (popmax 0.00187%, nfe); Associated with MN1-related disorder.

What condition is associated with MN1 p.Val1283= (c.3849C>T)?

MN1 p.Val1283= (c.3849C>T) is associated with MN1-related disorder (ClinVar).

How common is MN1 p.Val1283= (c.3849C>T) in the general population?

MN1 p.Val1283= (c.3849C>T) is very rare (popmax 0.00187%, nfe) (gnomAD).

MN1 p.Val1283=

c.3849C>T · rs373855008 · VCV3045067

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00187%, nfe)

Conditions

MN1-related disorder

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 0.94	GERP 0.75, phastCons 1
Overall
CADD	5.139	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00187% European (non-Finnish) · 22/1,177,316 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00137% 22/1,609,744 alleles · very rare exomes 19/1,457,476 · genomes 3/152,268 · 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: MN1
Protein: p.Val1283=
Coding: c.3849C>T
MANE Select: NM_002430
dbSNP: rs373855008
Type: single nucleotide variant
Location: chr22:27751029 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 42.47
Residue 1283: a UniProt-annotated variant site (in cebalid); a UniProt-annotated variant site (in cebalid; increased protein aggregation; decreased protein degradation via the ubiquitin-proteasome pathway; loss of interaction with ring1; decreased interaction with zbtb24; no effect on nuclear localization)

Full MN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MN1-related disorder

Similar variants

MN1 p.Gly915Arg Uncertain significance ★★ ⚠ same condition
MN1 p.Ser759Asn Uncertain significance ★★ ⚠ same condition
MN1 p.Gln436Ter Likely pathogenic ★ same condition
MN1 p.His258Leu Uncertain significance ★ ⚠ same condition
MN1 p.His310Arg Uncertain significance ★ ⚠ same condition
MN1 p.Pro1022Ser Uncertain significance ★ ⚠ same condition
MN1 p.Val846Met Uncertain significance ★ ⚠ same condition
MN1 p.Val1283fs Pathogenic same residue

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/mn1-p-val1283 (accessed [today's date]).

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