Is NEB p.Ser8038= (c.24114G>A) pathogenic?

NEB p.Ser8038= (c.24114G>A) is classified Uncertain significance in NEB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-08-11). Very rare (popmax 0.00149%, nfe); Associated with nemaline myopathy 2.

What condition is associated with NEB p.Ser8038= (c.24114G>A)?

NEB p.Ser8038= (c.24114G>A) is associated with nemaline myopathy 2, arthrogryposis multiplex congenita 6 (ClinVar).

How common is NEB p.Ser8038= (c.24114G>A) in the general population?

NEB p.Ser8038= (c.24114G>A) is very rare (popmax 0.00149%, nfe) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

NEB p.Ser8038=

c.24114G>A · rs781581005 · VCV1379855

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00149%, nfe)

Conditions

nemaline myopathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.77	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.65	loss · gain 0.24 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00149% European (non-Finnish) · 16/1,074,328 alleles

Filtering AF 0.000882% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000713%

Overall 0.00131% 19/1,448,378 alleles · very rare exomes 18/1,296,668 · genomes 1/151,710 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00178%	56,160
European (non-Finnish)grpmax	0.00149%	67,146
African / African-American	0.00143%	69,718
South Asian	0.00137%	72,998

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser8038=
Coding: c.24114G>A
MANE Select: NM_001164508
dbSNP: rs781581005
Type: single nucleotide variant
Location: chr2:151499298 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 8038: 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

Also linked: arthrogryposis multiplex congenita 6

For Severe congenital nemaline myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

NEB p.Ser8038Leu Uncertain significance ★★ same residue
NEB p.Ser8038fs 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-ser8038 (accessed [today's date]).

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