Is NBN p.Ser93= (c.279G>A) pathogenic?

NBN p.Ser93= (c.279G>A) is classified Benign/Likely benign in NBN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0717%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with NBN p.Ser93= (c.279G>A)?

NBN p.Ser93= (c.279G>A) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome (ClinVar).

How common is NBN p.Ser93= (c.279G>A) in the general population?

NBN p.Ser93= (c.279G>A) is ultra-rare (popmax 0.0717%, amr) (gnomAD).

NBN p.Ser93=

c.279G>A · rs587780781 · VCV136044

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0717%, amr)

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 0.88	GERP -2, phastCons 1
Overall
CADD	6.941	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0717% Admixed American · 43/60,002 alleles

Filtering AF 0.0546% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0486%

Overall 0.00477% 77/1,613,900 alleles · ultra-rare exomes 61/1,461,758 · genomes 16/152,142 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0717%	1,395
Finnishnot grpmax-eligible	0.0422%	2,370
African / African-American	0.00534%	18,726
European (non-Finnish)	0.000254%	393,331

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.Ser93=
Coding: c.279G>A
MANE Select: NM_002485
dbSNP: rs587780781
Type: single nucleotide variant
Location: chr8:89981416 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB
Residue 93: the 'disordered' region

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.Ser93Ter Pathogenic/Likely pathogenic ★★ same residue
NBN p.Ser93Ala Uncertain significance ★ ⚠ same residue
NBN p.Ser93Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
NBN p.Ser93Pro Uncertain significance ★ ⚠ same residue
NBN p.Ser93Trp 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

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-ser93 (accessed [today's date]).

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