Is NEB p.Val7834Phe (c.23500G>T) pathogenic?

NEB p.Val7834Phe (c.23500G>T) is classified Uncertain significance in NEB (ClinVar, Single submitter, 2 submitters; last evaluated 2017-09-13). AlphaMissense: ambiguous (0.3529); Very rare (popmax 0.000255%, nfe); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Val7834Phe (c.23500G>T)?

NEB p.Val7834Phe (c.23500G>T) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Val7834Phe (c.23500G>T) in the general population?

NEB p.Val7834Phe (c.23500G>T) is very rare (popmax 0.000255%, nfe) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about NEB p.Val7834Phe (c.23500G>T)?

AlphaMissense predicts ambiguous (score 0.3529) — an in-silico prediction, not a clinical call.

NEB p.Val7834Phe

c.23500G>T · rs1553601424 · VCV451955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3529 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Conditions

nemaline myopathy 2

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3529	ambiguous
REVEL	0.356	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V6133F vs ClinVar V7834F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000255% European (non-Finnish) · 3/1,178,406 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,611,480 alleles · very rare exomes 3/1,459,224 · genomes 0/152,256 · joint denominator

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: NEB
Protein: p.Val7834Phe
Coding: c.23500G>T
MANE Select: NM_001164508
dbSNP: rs1553601424
Type: single nucleotide variant
Location: chr2:151506965 (GRCh38)

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

Disease context

nemaline myopathy 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe congenital nemaline myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

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-val7834phe (accessed [today's date]).

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