Is LRTOMT p.Arg252= (c.756C>T) pathogenic?

LRTOMT p.Arg252= (c.756C>T) is classified Uncertain significance in LRTOMT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-24). Ultra-rare (popmax 0.0123%, afr).

How common is LRTOMT p.Arg252= (c.756C>T) in the general population?

LRTOMT p.Arg252= (c.756C>T) is ultra-rare (popmax 0.0123%, afr) (gnomAD).

LRTOMT p.Arg252=

c.756C>T · rs933205686 · VCV1300473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, afr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.25	GERP 0.85, phastCons 0.98
Overall
CADD	7.971	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0123% African / African-American · 9/73,060 alleles

Filtering AF 0.00638% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00478%

Overall 0.00058% 9/1,550,538 alleles · ultra-rare exomes 2/1,398,316 · genomes 7/152,222 · 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: LRTOMT
Protein: p.Arg252=
Coding: c.756C>T
dbSNP: rs933205686
Type: single nucleotide variant
Location: chr11:72108805 (GRCh38)

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

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/lrtomt-p-arg252 (accessed [today's date]).

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