Is MTR c.*16del pathogenic?

MTR c.16del is classified Benign in MTR (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-26). Common (popmax 40.1%, sas) — too common for a highly-penetrant pathogenic allele; Associated with methylcobalamin deficiency type cblG.

What condition is associated with MTR c.*16del?

MTR c.*16del is associated with methylcobalamin deficiency type cblG (ClinVar).

How is Homocystinuria without methylmalonic aciduria inherited?

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

MTR c.*16del

Q: How common is MTR c.*16del in the general population?

MTR c.*16del is common (popmax 40.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs67705775 · VCV296586

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 40.1%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

methylcobalamin deficiency type cblG

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.38	GERP -1.6
Overall
CADD	6.732	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(T)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 40.1% South Asian · 29,162/72,782 alleles

Filtering AF 39.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 39.5%

Overall 35.9% 468,275/1,304,924 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	40.1%	2
Remaining individualsnot grpmax-eligible	37.4%	3
Finnishnot grpmax-eligible	36.9%	3
Ashkenazi Jewishnot grpmax-eligible	36.5%	3
European (non-Finnish)	36.2%	3
East Asian	36.1%	3
Admixed American	32.9%	3
Middle Eastern	32.7%	3
African / African-American	27%	4
Amishnot grpmax-eligible	18.6%	5

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: MTR
Coding: c.*16del
MANE Select: NM_000254
dbSNP: rs67705775
Type: Deletion
Location: chr1:236897646 (GRCh38)
Gene constraint: LOEUF 0.625 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.60 · 9 PDB

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.Ala935fs Pathogenic ★★ same condition
MTR p.Ile1201fs Pathogenic ★★ same condition
MTR p.Ile881del Uncertain significance ★★ same condition
MTR c.2474-18_2474-17del Benign/Likely benign ★★ same condition
MTR c.2474-18del Benign ★★ same condition
MTR c.2474-19_2474-15del Likely benign ★★ same condition
MTR c.2044-1_2047del Likely pathogenic ★ same condition
MTR p.Ala128fs 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/mtr-c-star-16del (accessed [today's date]).

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