Is NEB p.Asp2829Glu (c.8487C>G) pathogenic?

NEB p.Asp2829Glu (c.8487C>G) is classified Uncertain significance in NEB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-26). AlphaMissense: likely benign (0.2478); Absent from gnomAD v4.1.

How common is NEB p.Asp2829Glu (c.8487C>G) in the general population?

NEB p.Asp2829Glu (c.8487C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NEB p.Asp2829Glu (c.8487C>G)?

AlphaMissense predicts likely benign (score 0.2478) — an in-silico prediction, not a clinical call.

NEB p.Asp2829Glu

c.8487C>G · rs1243027424 · VCV2434234

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2478 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.2478	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 1.4, phastCons 0.86
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 2.1e-05 · regional, not allelic
Overall
CADD	19.21	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NEB
Protein: p.Asp2829Glu
Coding: c.8487C>G
MANE Select: NM_001164508
dbSNP: rs1243027424
Type: single nucleotide variant
Location: chr2:151640553 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI <0.01 (gnomAD)
Residue 2829: a UniProt-annotated variant site (in amc6)

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

Similar variants

NEB p.Asp2829Asn Uncertain significance ★★ ⚠ same residue
NEB p.Asp2829= Likely benign ★ same residue
NEB c.11910+1G>A Likely pathogenic ★★★ same type
NEB c.6076-1G>T Likely pathogenic ★★★ same type
NEB c.78+1G>A Pathogenic ★★★ same type
NEB p.Arg2313Ter Pathogenic ★★★ same type
NEB p.Asp498Gly Likely pathogenic ★★★ ⚠ same type
NEB p.Ser6366Ile Pathogenic ★★★ same type

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-asp2829glu (accessed [today's date]).

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