Is NEB p.Pro2329Ser (c.6985C>T) pathogenic?

NEB p.Pro2329Ser (c.6985C>T) is classified Uncertain significance in NEB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: ambiguous (0.4762); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NEB p.Pro2329Ser (c.6985C>T)?

NEB p.Pro2329Ser (c.6985C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NEB p.Pro2329Ser (c.6985C>T) in the general population?

NEB p.Pro2329Ser (c.6985C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about NEB p.Pro2329Ser (c.6985C>T)?

AlphaMissense predicts ambiguous (score 0.4762) — an in-silico prediction, not a clinical call.

NEB p.Pro2329Ser

c.6985C>T · VCV4118386

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4762 · ACMG-weighted

gnomAD v4.1

Rare

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

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4762	ambiguous
REVEL	0.646	pathogenic-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 2.1e-05 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,812 alleles

Overall 6.84e-05% 1/1,461,592 alleles · very rare

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.Pro2329Ser
Coding: c.6985C>T
MANE Select: NM_001164508
Type: single nucleotide variant
Location: chr2:151650816 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 2329: 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

Similar variants

NEB p.Pro2329Leu Uncertain significance ★ same residue
NEB p.Pro2329= Likely benign ★ same residue
NEB c.5344-1G>C Likely pathogenic ★★ same condition
NEB p.Ala1070Val Uncertain significance ★★ ⚠ same condition
NEB p.Ala1807Ser Uncertain significance ★★ ⚠ same condition
NEB p.Ala1823Ser Uncertain significance ★★ ⚠ same condition
NEB p.Ala1906Val Uncertain significance ★★ ⚠ same condition
NEB p.Ala251Pro 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-pro2329ser (accessed [today's date]).

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