Is NEB p.Ser8486Phe (c.25457C>T) pathogenic?

NEB p.Ser8486Phe (c.25457C>T) is classified Uncertain significance in NEB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: ambiguous (0.4084); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NEB p.Ser8486Phe (c.25457C>T)?

NEB p.Ser8486Phe (c.25457C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NEB p.Ser8486Phe (c.25457C>T) in the general population?

NEB p.Ser8486Phe (c.25457C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NEB p.Ser8486Phe (c.25457C>T)?

AlphaMissense predicts ambiguous (score 0.4084) — an in-silico prediction, not a clinical call.

NEB p.Ser8486Phe

c.25457C>T · VCV3403951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4084 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4084	ambiguous
REVEL	0.833	moderately 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 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	26.0	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 S6630F vs ClinVar S8486F) — verify the residue.

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.Ser8486Phe
Coding: c.25457C>T
MANE Select: NM_001164508
Type: single nucleotide variant
Location: chr2:151485881 (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

Similar variants

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
NEB p.Ala2541Thr Uncertain significance ★★ ⚠ same condition
NEB p.Ala2643Gly 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-ser8486phe (accessed [today's date]).

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