Is MTR p.Asp915Glu (c.2745T>G) pathogenic?

MTR p.Asp915Glu (c.2745T>G) is classified Uncertain significance in MTR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-14). AlphaMissense: likely benign (0.104); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MTR p.Asp915Glu (c.2745T>G)?

MTR p.Asp915Glu (c.2745T>G) is associated with Inborn genetic diseases (ClinVar).

How common is MTR p.Asp915Glu (c.2745T>G) in the general population?

MTR p.Asp915Glu (c.2745T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTR p.Asp915Glu (c.2745T>G)?

AlphaMissense predicts likely benign (score 0.104) — an in-silico prediction, not a clinical call.

MTR p.Asp915Glu

c.2745T>G · rs2528436271 · VCV2267226

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.104 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.104	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -4.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.31	GERP -0.85, phastCons 0.35
Regional constraint	o/e 0.81	unconstrained · MANE · 102 kb · p 9.3e-14 · regional, not allelic
Overall
CADD	5.637	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: MTR
Protein: p.Asp915Glu
Coding: c.2745T>G
MANE Select: NM_000254
dbSNP: rs2528436271
Type: single nucleotide variant
Location: chr1:236885189 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MTR p.Asp915Val Uncertain significance ★ ⚠ same residue
MTR p.Ala205Val Uncertain significance ★★ same condition
MTR p.Ala442Glu Uncertain significance ★★ ⚠ same condition
MTR p.Arg1029Trp Uncertain significance ★★ ⚠ same condition
MTR p.Arg220Gln Uncertain significance ★★ ⚠ same condition
MTR p.Arg220Trp Uncertain significance ★★ ⚠ same condition
MTR p.Arg43Gln Uncertain significance ★★ ⚠ same condition
MTR p.Arg43Trp Uncertain significance ★★ ⚠ 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-asp915glu (accessed [today's date]).

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