Is NBN p.Ser355= (c.1065C>T) pathogenic?

NBN p.Ser355= (c.1065C>T) is classified Likely benign in NBN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-15). Ultra-rare (popmax 0.0164%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with NBN p.Ser355= (c.1065C>T)?

NBN p.Ser355= (c.1065C>T) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome (ClinVar).

How common is NBN p.Ser355= (c.1065C>T) in the general population?

NBN p.Ser355= (c.1065C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

NBN p.Ser355=

c.1065C>T · rs876659205 · VCV231519

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.67	GERP -3.8
Overall
CADD	5.739	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00211% 34/1,613,934 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
European (non-Finnish)	0.00254%	39,332
East Asian	0.00223%	44,890
African / African-American	0.00134%	74,902

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.Ser355=
Coding: c.1065C>T
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs876659205
Type: single nucleotide variant
Location: chr8:89958784 (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.Ser355Cys Uncertain significance ★★ ⚠ same residue
NBN p.Ser355Gly Uncertain significance ★★ ⚠ same residue
NBN p.Ser355Arg Uncertain significance ★ ⚠ same residue
NBN p.Ser355Asn Uncertain significance ★ ⚠ 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

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-ser355 (accessed [today's date]).

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