Is NEB p.Phe8324Ser (c.24971T>C) pathogenic?

NEB p.Phe8324Ser (c.24971T>C) is classified Uncertain significance in NEB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). AlphaMissense: likely pathogenic (0.7372); Absent from gnomAD v4.1; Associated with nemaline myopathy 2.

What condition is associated with NEB p.Phe8324Ser (c.24971T>C)?

NEB p.Phe8324Ser (c.24971T>C) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Phe8324Ser (c.24971T>C) in the general population?

NEB p.Phe8324Ser (c.24971T>C) is absent from gnomAD v4.1 (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.Phe8324Ser (c.24971T>C)?

AlphaMissense predicts likely pathogenic (score 0.7372) — an in-silico prediction, not a clinical call.

NEB p.Phe8324Ser

c.24971T>C · rs2057142099 · VCV2060556

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7372 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

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	0.7372	likely pathogenic
REVEL	0.819	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F6468S vs ClinVar F8324S) — verify the residue.

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.Phe8324Ser
Coding: c.24971T>C
MANE Select: NM_001164508
dbSNP: rs2057142099
Type: single nucleotide variant
Location: chr2:151492184 (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-phe8324ser (accessed [today's date]).

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