Is MTR p.Ser1083fs (c.3247_3248del) pathogenic?

MTR p.Ser1083fs (c.32473248del) is classified Pathogenic in MTR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-24). Absent from gnomAD; Associated with methylcobalamin deficiency type cblG.

What condition is associated with MTR p.Ser1083fs (c.3247_3248del)?

MTR p.Ser1083fs (c.3247_3248del) is associated with methylcobalamin deficiency type cblG (ClinVar).

How common is MTR p.Ser1083fs (c.3247_3248del) in the general population?

MTR p.Ser1083fs (c.3247_3248del) is absent from gnomAD (gnomAD).

How is Homocystinuria without methylmalonic aciduria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MTR p.Ser1083fs

c.3247_3248del · rs2528522105 · VCV2746182

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

methylcobalamin deficiency type cblG

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 30 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	GERP -2.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MTR
Protein: p.Ser1083fs
Coding: c.3247_3248del
MANE Select: NM_000254
dbSNP: rs2528522105
Type: Microsatellite
Location: chr1:236894396 (GRCh38)
Gene constraint: LOEUF 0.625 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.60 · 9 PDB
Residue 1083: an α-helix; the adomet activation domain

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

Disease context

methylcobalamin deficiency type cblG — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Homocystinuria without methylmalonic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

MTR p.Val890fs Pathogenic ★★ same condition
MTR c.409+15_409+17del Likely benign ★★ same condition
MTR p.Arg755fs Pathogenic ★ same condition
MTR p.Ile687fs Pathogenic ★ same condition
MTR p.Thr1184fs Pathogenic ★ same condition
MTR p.Glu503del Uncertain significance ★ same condition
MTR c.1189-17_1189-14del Likely benign ★ same condition
MTR c.3008-19_3008-14del Likely benign ★ 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/mtr-p-ser1083fs (accessed [today's date]).

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