Is LMNA p.Ile26Val (c.76A>G) pathogenic?

LMNA p.Ile26Val (c.76A>G) is classified Uncertain significance in LMNA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-03). AlphaMissense: likely pathogenic (0.6794); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with LMNA p.Ile26Val (c.76A>G)?

LMNA p.Ile26Val (c.76A>G) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is LMNA p.Ile26Val (c.76A>G) in the general population?

LMNA p.Ile26Val (c.76A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LMNA p.Ile26Val (c.76A>G)?

AlphaMissense predicts likely pathogenic (score 0.6794) — an in-silico prediction, not a clinical call.

LMNA p.Ile26Val

c.76A>G · rs1302425397 · VCV1720742

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6794 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
AlphaMissense	0.6794	likely pathogenic
REVEL	0.295	indeterminate
SaProt	LLR -6.03	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 21 kb · p 3e-16 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

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: LMNA
Protein: p.Ile26Val
Coding: c.76A>G
MANE Select: NM_170707
dbSNP: rs1302425397
Type: single nucleotide variant
Location: chr1:156114994 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 28 PDB
Residue 26: a β-strand; the 'interaction with mlip' region; the 'head' 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.Ile26= Conflicting classifications of pathogenicity ★ same residue
LMNA p.Ile26Thr Uncertain significance ★★ ⚠ same residue
LMNA p.Ile26Leu 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

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-ile26val (accessed [today's date]).

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