Is LMNA p.Arg7= (c.21G>A) pathogenic?

LMNA p.Arg7= (c.21G>A) is classified Likely benign in LMNA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-26). Very rare (popmax 7.08e-05%); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with LMNA p.Arg7= (c.21G>A)?

LMNA p.Arg7= (c.21G>A) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is LMNA p.Arg7= (c.21G>A) in the general population?

LMNA p.Arg7= (c.21G>A) is very rare (popmax 7.08e-05%) (gnomAD).

LMNA p.Arg7=

c.21G>A · rs2102816901 · VCV2918764

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 7.08e-05%)

Conditions

Charcot-Marie-Tooth disease type 2

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 8.3	GERP 1.2, phastCons 1
Overall
CADD	15.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.08e-05%

Overall 7.08e-05% 1/1,412,360 alleles · very rare

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: LMNA
Protein: p.Arg7=
Coding: c.21G>A
MANE Select: NM_170707
dbSNP: rs2102816901
Type: single nucleotide variant
Location: chr1:156114939 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 28 PDB
Residue 7: the 'interaction with mlip' region; the 'head' region; the 'disordered' region

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

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LMNA p.Arg7Gln Uncertain significance ★★ ⚠ same residue
LMNA p.Arg7Trp Uncertain significance ★★ ⚠ same residue
LMNA c.1157+1G>A Pathogenic/Likely pathogenic ★★ same condition
LMNA c.1157+1G>T Pathogenic/Likely pathogenic ★★ same condition
LMNA c.1380+1G>A Pathogenic ★★ same condition
LMNA c.1489-2A>G Likely pathogenic ★★ same condition
LMNA c.1608+1G>A Pathogenic ★★ same condition
LMNA c.1608+2T>G Pathogenic/Likely 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/lmna-p-arg7 (accessed [today's date]).

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