Is LARGE1 p.Arg70= (c.210C>T) pathogenic?

LARGE1 p.Arg70= (c.210C>T) is classified Conflicting classifications of pathogenicity in LARGE1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-28). Rare (popmax 0.666%, afr); Associated with muscular dystrophy-dystroglycanopathy type B6.

What condition is associated with LARGE1 p.Arg70= (c.210C>T)?

LARGE1 p.Arg70= (c.210C>T) is associated with muscular dystrophy-dystroglycanopathy type B6 (ClinVar).

How common is LARGE1 p.Arg70= (c.210C>T) in the general population?

LARGE1 p.Arg70= (c.210C>T) is rare (popmax 0.666%, afr) (gnomAD).

LARGE1 p.Arg70=

c.210C>T · rs145048151 · VCV167253

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.666%, afr)

Conditions

muscular dystrophy-dystroglycanopathy type B6

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 -9.5	GERP -4.2
Overall
CADD	0.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.666% African / African-American · 500/75,042 alleles

Filtering AF 0.618% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.599%

Overall 0.0358% 575/1,607,776 alleles · rare exomes 269/1,455,452 · genomes 306/152,324 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.666%	150
Admixed American	0.0617%	1,622
Remaining individualsnot grpmax-eligible	0.0464%	2,154
East Asian	0.00223%	44,872
European (non-Finnish)	0.000678%	147,486

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: LARGE1
Protein: p.Arg70=
Coding: c.210C>T
MANE Select: NM_133642
dbSNP: rs145048151
Type: single nucleotide variant
Location: chr22:33650565 (GRCh38)
Gene constraint: LOEUF 0.606 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.15 · 4 PDB

Full LARGE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

muscular dystrophy-dystroglycanopathy type B6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LARGE1 p.Arg95Ter Pathogenic ★★ same condition
LARGE1 p.Glu509Lys Pathogenic/Likely pathogenic ★★ same condition
LARGE1 c.*155C>T Uncertain significance ★★ same condition
LARGE1 p.Ala149Ser Uncertain significance ★★ ⚠ same condition
LARGE1 p.Ala252Val Uncertain significance ★★ ⚠ same condition
LARGE1 p.Ala478Thr Uncertain significance ★★ ⚠ same condition
LARGE1 p.Ala635Thr Uncertain significance ★★ ⚠ same condition
LARGE1 p.Ala752Gly 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/large1-p-arg70 (accessed [today's date]).

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