Is NBN p.Ser387Cys (c.1160C>G) pathogenic?

NBN p.Ser387Cys (c.1160C>G) is classified Conflicting classifications of pathogenicity in NBN (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2023-04-18). AlphaMissense: likely benign (0.0759); Ultra-rare (popmax 0.0571%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with NBN p.Ser387Cys (c.1160C>G)?

NBN p.Ser387Cys (c.1160C>G) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome (ClinVar).

How common is NBN p.Ser387Cys (c.1160C>G) in the general population?

NBN p.Ser387Cys (c.1160C>G) is ultra-rare (popmax 0.0571%, sas) (gnomAD).

What do computational predictors say about NBN p.Ser387Cys (c.1160C>G)?

AlphaMissense predicts likely benign (score 0.0759) — an in-silico prediction, not a clinical call.

NBN p.Ser387Cys

c.1160C>G · rs747632184 · VCV232200

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0759 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0571%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0759	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -9.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1
Overall
CADD	8.48	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

Grpmax group 0.0571% South Asian · 52/91,046 alleles

Filtering AF 0.0447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0403%

Overall 0.00322% 52/1,613,258 alleles · ultra-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: NBN
Protein: p.Ser387Cys
Coding: c.1160C>G
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs747632184
Type: single nucleotide variant
Location: chr8:89955520 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Nijmegen breakage syndrome

Similar variants

NBN p.Ser387= Likely benign ★★ same residue
NBN c.1124+1G>C Likely pathogenic ★★ same condition
NBN c.1124+2T>G Likely pathogenic ★★ same condition
NBN c.1397+2T>A Likely pathogenic ★★ same condition
NBN c.171+1G>A Likely pathogenic ★★ same condition
NBN c.172-1G>T Likely pathogenic ★★ same condition
NBN c.172-2A>G Likely pathogenic ★★ same condition
NBN c.1845+1G>A Likely 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/nbn-p-ser387cys (accessed [today's date]).

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