Is NEB p.Pro1904= (c.5712T>C) pathogenic?

NEB p.Pro1904= (c.5712T>C) is classified Likely benign in NEB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-06). Ultra-rare (popmax 0.0986%, afr); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Pro1904= (c.5712T>C)?

NEB p.Pro1904= (c.5712T>C) is associated with nemaline myopathy 2 (ClinVar).

How common is NEB p.Pro1904= (c.5712T>C) in the general population?

NEB p.Pro1904= (c.5712T>C) is ultra-rare (popmax 0.0986%, afr) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

NEB p.Pro1904=

c.5712T>C · rs35946547 · VCV714462

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0986%, afr)

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 -3.2	GERP -2.9
Overall
CADD	1.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0986% African / African-American · 74/75,038 alleles

Filtering AF 0.0805% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0739%

Overall 0.00527% 85/1,613,424 alleles · ultra-rare exomes 37/1,461,090 · genomes 48/152,334 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0986%	1,014
Remaining individualsnot grpmax-eligible	0.00961%	10,411
Admixed American	0.00833%	11,998

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.Pro1904=
Coding: c.5712T>C
MANE Select: NM_001164508
dbSNP: rs35946547
Type: single nucleotide variant
Location: chr2:151663599 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 1904: 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-pro1904 (accessed [today's date]).

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