Is NEB p.Ala247= (c.741T>C) pathogenic?

NEB p.Ala247= (c.741T>C) is classified Likely benign in NEB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-08). Absent from gnomAD v4.1; Associated with nemaline myopathy 2.

What condition is associated with NEB p.Ala247= (c.741T>C)?

NEB p.Ala247= (c.741T>C) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Ala247= (c.741T>C) in the general population?

NEB p.Ala247= (c.741T>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.

NEB p.Ala247=

c.741T>C · rs760286086 · VCV2915035

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,898)

Conditions

nemaline myopathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.8, phastCons 0.053
Overall
CADD	10.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,898). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NEB
Protein: p.Ala247=
Coding: c.741T>C
MANE Select: NM_001164508
dbSNP: rs760286086
Type: single nucleotide variant
Location: chr2:151717497 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)

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.Ala247Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
NEB p.Ala247fs Pathogenic/Likely pathogenic ★★ same residue
NEB p.Ala247Ser 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-ala247 (accessed [today's date]).

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