Is NEB p.Pro7370Arg (c.22109C>G) pathogenic?

NEB p.Pro7370Arg (c.22109C>G) is classified Conflicting classifications of pathogenicity in NEB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-11). AlphaMissense: likely benign (0.3062); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NEB p.Pro7370Arg (c.22109C>G)?

NEB p.Pro7370Arg (c.22109C>G) is associated with Inborn genetic diseases, nemaline myopathy 2 (ClinVar).

How common is NEB p.Pro7370Arg (c.22109C>G) in the general population?

NEB p.Pro7370Arg (c.22109C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about NEB p.Pro7370Arg (c.22109C>G)?

AlphaMissense predicts likely benign (score 0.3062) — an in-silico prediction, not a clinical call.

NEB p.Pro7370Arg

c.22109C>G · rs766467431 · VCV2275348

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3062 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3062	likely benign
REVEL	0.37	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P5669R vs ClinVar P7370R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,884 alleles

Overall 0.000867% 14/1,613,892 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,277
European (non-Finnish)grpmax	8.48e-05%	1,179,884

Ashkenazi Jewish 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.Pro7370Arg
Coding: c.22109C>G
MANE Select: NM_001164508
dbSNP: rs766467431
Type: single nucleotide variant
Location: chr2:151526010 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 7370: a UniProt-annotated variant site (in amc6)

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

Similar variants

NEB p.Pro7370= Conflicting classifications of pathogenicity ★ same residue
NEB p.Pro7370Ala 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-pro7370arg (accessed [today's date]).

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