Is NEB p.Phe7153Val (c.21457T>G) pathogenic?

NEB p.Phe7153Val (c.21457T>G) is classified Uncertain significance in NEB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-19). AlphaMissense: likely pathogenic (0.6312); Absent from gnomAD v4.1; Associated with nemaline myopathy 2.

What condition is associated with NEB p.Phe7153Val (c.21457T>G)?

NEB p.Phe7153Val (c.21457T>G) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Phe7153Val (c.21457T>G) in the general population?

NEB p.Phe7153Val (c.21457T>G) 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.Phe7153Val (c.21457T>G)?

AlphaMissense predicts likely pathogenic (score 0.6312) — an in-silico prediction, not a clinical call.

NEB p.Phe7153Val

c.21457T>G · rs2153501601 · VCV1388950

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6312 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

nemaline myopathy 2

Computational evidence

Protein change
AlphaMissense	0.6312	likely pathogenic
REVEL	0.27	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, 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 F5452V vs ClinVar F7153V) — 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.Phe7153Val
Coding: c.21457T>G
MANE Select: NM_001164508
dbSNP: rs2153501601
Type: single nucleotide variant
Location: chr2:151531857 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 7153: a UniProt-annotated variant site (in amc6)

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)

Similar variants

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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
NEB p.Ser6366Ile Pathogenic ★★★ same condition
NEB p.Ser6648= Pathogenic ★★★ same condition
NEB c.22590+2T>C 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/neb-p-phe7153val (accessed [today's date]).

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