Is NEB p.Val2862Phe (c.8584G>T) pathogenic?

NEB p.Val2862Phe (c.8584G>T) is classified Uncertain significance in NEB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-29). AlphaMissense: likely pathogenic (0.6847); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NEB p.Val2862Phe (c.8584G>T)?

NEB p.Val2862Phe (c.8584G>T) is associated with Inborn genetic diseases, nemaline myopathy 2 (ClinVar).

How common is NEB p.Val2862Phe (c.8584G>T) in the general population?

NEB p.Val2862Phe (c.8584G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NEB p.Val2862Phe (c.8584G>T)?

AlphaMissense predicts likely pathogenic (score 0.6847) — an in-silico prediction, not a clinical call.

NEB p.Val2862Phe

c.8584G>T · rs949616238 · VCV1431600

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6847 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6847	likely pathogenic
REVEL	0.353	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 2.1e-05 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: NEB
Protein: p.Val2862Phe
Coding: c.8584G>T
MANE Select: NM_001164508
dbSNP: rs949616238
Type: single nucleotide variant
Location: chr2:151640456 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 2862: a UniProt-annotated variant site (in amc6)

Full NEB 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

Also linked: nemaline myopathy 2

Similar variants

NEB p.Val2862= Likely benign ★ same residue
NEB p.Val2862fs Pathogenic ★ same residue
NEB p.Val2862Ile Uncertain significance ★ ⚠ same residue
NEB c.11910+1G>A Likely pathogenic ★★★ same condition
NEB c.6076-1G>T Likely pathogenic ★★★ same condition
NEB c.78+1G>A Pathogenic ★★★ same condition
NEB p.Arg2313Ter Pathogenic ★★★ same condition
NEB p.Asp498Gly 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/neb-p-val2862phe (accessed [today's date]).

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