Is NEFL p.Gln537= (c.1611A>G) pathogenic?

NEFL p.Gln537= (c.1611A>G) is classified Likely benign in NEFL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-11-01). Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease.

What condition is associated with NEFL p.Gln537= (c.1611A>G)?

NEFL p.Gln537= (c.1611A>G) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 2E (ClinVar).

How common is NEFL p.Gln537= (c.1611A>G) in the general population?

NEFL p.Gln537= (c.1611A>G) is absent from gnomAD v4.1 (gnomAD).

NEFL p.Gln537=

c.1611A>G · rs1802987929 · VCV916902

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Charcot-Marie-Tooth disease

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 -0.65	GERP -0.51, phastCons 0.004
Overall
CADD	3.479	PHRED · no single calibrated threshold — expert panels disagree

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: NEFL
Protein: p.Gln537=
Coding: c.1611A>G
MANE Select: NM_006158
dbSNP: rs1802987929
Type: single nucleotide variant
Location: chr8:24952831 (GRCh38)
Gene constraint: LOEUF 0.986 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.66
Residue 537: the 'tail' region; the 'tail, subdomain b (acidic)' region; the 'disordered' region

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

Disease context

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

Also linked: Charcot-Marie-Tooth disease type 2E

Similar variants

NEFL p.Gln537Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
NEFL p.Arg399Ter Pathogenic/Likely pathogenic ★★ same condition
NEFL p.Arg421Ter Pathogenic ★★ same condition
NEFL p.Asn98Ser Pathogenic/Likely pathogenic ★★ same condition
NEFL p.Glu186Ter Pathogenic/Likely pathogenic ★★ same condition
NEFL p.Glu396Lys Pathogenic ★★ same condition
NEFL p.Glu90Lys Pathogenic ★★ same condition
NEFL p.Pro22Ser 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/nefl-p-gln537 (accessed [today's date]).

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