Is NEB p.Asp4271= (c.12813T>C) pathogenic?

NEB p.Asp4271= (c.12813T>C) is classified Likely benign in NEB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-26). Very rare (popmax 0.00663%, sas); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Asp4271= (c.12813T>C)?

NEB p.Asp4271= (c.12813T>C) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Asp4271= (c.12813T>C) in the general population?

NEB p.Asp4271= (c.12813T>C) is very rare (popmax 0.00663%, sas) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

NEB p.Asp4271=

c.12813T>C · rs2097626924 · VCV1130577

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00663%, sas)

Conditions

nemaline myopathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.13	GERP -3.7, phastCons 0.063
Overall
CADD	4.186	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00663% South Asian · 3/45,280 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000887%

Overall 0.00176% 9/510,680 alleles · very rare exomes 9/455,930 · genomes 0/54,750 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00663%	15,093
Remaining individualsnot grpmax-eligible	0.00397%	25,202
European (non-Finnish)	0.00155%	64,622

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.Asp4271=
Coding: c.12813T>C
MANE Select: NM_001164508
dbSNP: rs2097626924
Type: single nucleotide variant
Location: chr2:151604806 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 4271: 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 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
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-asp4271 (accessed [today's date]).

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