Is NEFH p.Pro1007Ser (c.3019C>T) pathogenic?

NEFH p.Pro1007Ser (c.3019C>T) is classified Likely benign in NEFH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-21). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NEFH p.Pro1007Ser (c.3019C>T)?

NEFH p.Pro1007Ser (c.3019C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NEFH p.Pro1007Ser (c.3019C>T) in the general population?

NEFH p.Pro1007Ser (c.3019C>T) is absent from gnomAD v4.1 (gnomAD).

NEFH p.Pro1007Ser

c.3019C>T · rs2517980050 · VCV2480962

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.296	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1, phastCons 0.94
Regional constraint	o/e 0.87	unconstrained · MANE · 895 bp · p 0.014 · regional, not allelic
Overall
CADD	14.29	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: NEFH
Protein: p.Pro1007Ser
Coding: c.3019C>T
MANE Select: NM_021076
dbSNP: rs2517980050
Type: single nucleotide variant
Location: chr22:29490659 (GRCh38)
Gene constraint: LOEUF 1.417 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 1007: the 'tail' region; the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NEFH p.Pro1007Leu Likely benign ★ same residue
NEFH p.Pro1007Thr Uncertain significance ★ same residue
NEFH c.1209-2A>G Uncertain significance ★★ same condition
NEFH p.Ala103Thr Uncertain significance ★★ same condition
NEFH p.Ala141Thr Uncertain significance ★★ same condition
NEFH p.Ala189Val Uncertain significance ★★ same condition
NEFH p.Ala203Thr Uncertain significance ★★ same condition
NEFH p.Ala220Val 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/nefh-p-pro1007ser (accessed [today's date]).

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