Is NBN p.Asp399= (c.1197T>C) pathogenic?

NBN p.Asp399= (c.1197T>C) is classified Benign/Likely benign in NBN (ClinVar, Multiple submitters, 20 submitters; last evaluated 2026-02-04). Common (popmax 77.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary neoplastic syndrome.

What condition is associated with NBN p.Asp399= (c.1197T>C)?

NBN p.Asp399= (c.1197T>C) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, acute lymphoblastic leukemia (ClinVar).

NBN p.Asp399=

Q: How common is NBN p.Asp399= (c.1197T>C) in the general population?

NBN p.Asp399= (c.1197T>C) is common (popmax 77.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1197T>C · rs709816 · VCV183701

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 20 submitters

gnomAD v4.1

Common

common (popmax 77.6%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.27	GERP -3.4
Overall
CADD	0.766	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 77.6% African / African-American · 58,081/74,864 alleles

Filtering AF 77.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 76.8%

Overall 40.9% 659,535/1,612,850 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	77.6%	1
East Asian	67.8%	1
Admixed American	56.1%	2
South Asian	51.3%	2
Finnishnot grpmax-eligible	43.7%	2
Remaining individualsnot grpmax-eligible	42.7%	2
Middle Eastern	39%	3
European (non-Finnish)	35.9%	3
Ashkenazi Jewishnot grpmax-eligible	35.3%	3
Amishnot grpmax-eligible	31.1%	3

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.Asp399=
Coding: c.1197T>C
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs709816
Type: single nucleotide variant
Location: chr8:89955483 (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: hereditary breast ovarian cancer syndrome acute lymphoblastic leukemia Nijmegen breakage syndrome

Similar variants

NBN p.Asp399Gly Uncertain significance ★ ⚠ same residue
NBN p.Asp399Asn 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
NBN c.172-1G>T Likely pathogenic ★★ same condition
NBN c.172-2A>G 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-asp399 (accessed [today's date]).

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