Is NEB p.Asp6922= (c.20766C>T) pathogenic?

NEB p.Asp6922= (c.20766C>T) is classified Benign in NEB (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Low-frequency (popmax 3.96%, sas); Associated with arthrogryposis multiplex congenita 6.

What condition is associated with NEB p.Asp6922= (c.20766C>T)?

NEB p.Asp6922= (c.20766C>T) is associated with arthrogryposis multiplex congenita 6, nemaline myopathy 2 (ClinVar).

How common is NEB p.Asp6922= (c.20766C>T) in the general population?

NEB p.Asp6922= (c.20766C>T) is low-frequency (popmax 3.96%, sas) (gnomAD).

NEB p.Asp6922=

c.20766C>T · rs34555492 · VCV129723

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.96%, sas)

Conditions

arthrogryposis multiplex congenita 6

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 -10	GERP -4.2
Overall
CADD	0.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.96% South Asian · 3,605/91,062 alleles

Filtering AF 3.85% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.81%

Overall 1.94% 31,298/1,613,436 alleles · low-frequency exomes 29,301/1,461,226 · genomes 1,997/152,210 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	3.96%	25
European (non-Finnish)	2.15%	46
Remaining individualsnot grpmax-eligible	1.82%	55
Middle Eastern	1.73%	58
Amishnot grpmax-eligible	0.877%	114
Finnishnot grpmax-eligible	0.617%	162
Admixed American	0.563%	177
African / African-American	0.387%	259
Ashkenazi Jewishnot grpmax-eligible	0.0845%	1,184
East Asian	0.0156%	6,408

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.Asp6922=
Coding: c.20766C>T
MANE Select: NM_001164508
dbSNP: rs34555492
Type: single nucleotide variant
Location: chr2:151540718 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 6922: a UniProt-annotated variant site (in amc6)

Full NEB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arthrogryposis multiplex congenita 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nemaline myopathy 2

Similar variants

NEB p.Asp6922Val Uncertain significance ★★ ⚠ same residue
NEB p.Asp6922Glu 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
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-asp6922 (accessed [today's date]).

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