Is NEB p.Phe7500= (c.22500C>T) pathogenic?

NEB p.Phe7500= (c.22500C>T) is classified Likely benign in NEB (ClinVar, Single submitter, 2 submitters; last evaluated 2025-07-15). Very rare (popmax 0.00446%, eas); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Phe7500= (c.22500C>T)?

NEB p.Phe7500= (c.22500C>T) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Phe7500= (c.22500C>T) in the general population?

NEB p.Phe7500= (c.22500C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

NEB p.Phe7500=

c.22500C>T · rs772294501 · VCV1125970

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

nemaline myopathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.125	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -5.5
Overall
CADD	5.514	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,812 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.00112% 18/1,610,878 alleles · very rare exomes 13/1,458,966 · genomes 5/151,912 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,406
African / African-American	0.00402%	24,906
Admixed American	0.00334%	29,980
European (non-Finnish)	0.000934%	107,056

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.Phe7500=
Coding: c.22500C>T
MANE Select: NM_001164508
dbSNP: rs772294501
Type: single nucleotide variant
Location: chr2:151519748 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 7500: 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

NEB p.Phe7500Leu Uncertain significance ★ ⚠ same residue
NEB p.Phe7500fs Likely pathogenic ★ 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
NEB p.Ser6366Ile 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-phe7500 (accessed [today's date]).

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