Is NEB p.Arg6287Cys (c.18859C>T) pathogenic?

NEB p.Arg6287Cys (c.18859C>T) is classified Conflicting classifications of pathogenicity in NEB (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.1015); Ultra-rare (popmax 0.0103%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NEB p.Arg6287Cys (c.18859C>T)?

NEB p.Arg6287Cys (c.18859C>T) is associated with Inborn genetic diseases, nemaline myopathy 2, arthrogryposis multiplex congenita 6 (ClinVar).

How common is NEB p.Arg6287Cys (c.18859C>T) in the general population?

NEB p.Arg6287Cys (c.18859C>T) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

What do computational predictors say about NEB p.Arg6287Cys (c.18859C>T)?

AlphaMissense predicts likely benign (score 0.1015) — an in-silico prediction, not a clinical call.

NEB p.Arg6287Cys

c.18859C>T · rs374606967 · VCV646996

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1015 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1015	likely benign
REVEL	0.293	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.25, phastCons 0.81
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	18.53	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R4586C vs ClinVar R6287C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0103% European (non-Finnish) · 120/1,161,032 alleles

Filtering AF 0.00881% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00825%

Overall 0.00837% 133/1,589,310 alleles · ultra-rare exomes 119/1,437,234 · genomes 14/152,076 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0103%	9,675
Ashkenazi Jewishnot grpmax-eligible	0.00686%	14,582
African / African-American	0.00671%	14,906
Remaining individualsnot grpmax-eligible	0.00652%	15,329
Admixed American	0.00168%	59,444
South Asian	0.00112%	89,098

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.Arg6287Cys
Coding: c.18859C>T
MANE Select: NM_001164508
dbSNP: rs374606967
Type: single nucleotide variant
Location: chr2:151562643 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nemaline myopathy 2 arthrogryposis multiplex congenita 6

Similar variants

NEB p.Arg6287= Benign/Likely benign ★★ same residue
NEB p.Arg6287His Conflicting classifications of pathogenicity ★ ⚠ 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-arg6287cys (accessed [today's date]).

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