Is NEBL p.Pro640Ser (c.1918C>T) pathogenic?

NEBL p.Pro640Ser (c.1918C>T) is classified Uncertain significance in NEBL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely benign (0.1776); Absent from gnomAD v4.1.

How common is NEBL p.Pro640Ser (c.1918C>T) in the general population?

NEBL p.Pro640Ser (c.1918C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NEBL p.Pro640Ser (c.1918C>T)?

AlphaMissense predicts likely benign (score 0.1776) — an in-silico prediction, not a clinical call.

NEBL p.Pro640Ser

c.1918C>T · VCV4118421

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1776 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1776	likely benign
REVEL	0.302	indeterminate
SaProt	LLR -12.63	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.8, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 111 kb · p 7.4e-07 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

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

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: NEBL
Protein: p.Pro640Ser
Coding: c.1918C>T
MANE Select: NM_006393
Type: single nucleotide variant
Location: chr10:20823252 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB

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

Similar variants

NEBL c.1227+5G>A Uncertain significance ★★ same type
NEBL c.1870-1G>A Uncertain significance ★★ same type
NEBL c.798+1G>A Uncertain significance ★★ same type
NEBL c.903+1G>T Uncertain significance ★★ same type
NEBL p.Ala114Ser Uncertain significance ★★ ⚠ same type
NEBL p.Ala209Ser Uncertain significance ★★ ⚠ same type
NEBL p.Ala219Thr Uncertain significance ★★ ⚠ same type
NEBL p.Ala264Val Uncertain significance ★★ ⚠ 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/nebl-p-pro640ser (accessed [today's date]).

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