Is NBN p.Asp121Val (c.362A>T) pathogenic?

NBN p.Asp121Val (c.362A>T) is classified Uncertain significance in NBN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-25). AlphaMissense: likely benign (0.2844); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with NBN p.Asp121Val (c.362A>T)?

NBN p.Asp121Val (c.362A>T) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome (ClinVar).

How common is NBN p.Asp121Val (c.362A>T) in the general population?

NBN p.Asp121Val (c.362A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NBN p.Asp121Val (c.362A>T)?

AlphaMissense predicts likely benign (score 0.2844) — an in-silico prediction, not a clinical call.

NBN p.Asp121Val

c.362A>T · rs770163751 · VCV2115075

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2844 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2844	likely benign
REVEL	0.644	pathogenic-leaning
SaProt	LLR -14.47	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.40	acceptor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 6.1	GERP 1.8, phastCons 1
Overall
CADD	25.9	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: NBN
Protein: p.Asp121Val
Coding: c.362A>T
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs770163751
Type: single nucleotide variant
Location: chr8:89980852 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB
Residue 121: 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.Asp121Glu Uncertain significance ★★ ⚠ same residue
NBN p.Asp121Gly Uncertain significance ★★ ⚠ same residue
NBN p.Asp121His Uncertain significance ★★ same residue
NBN p.Asp121Tyr Uncertain significance ★★ same residue
NBN p.Asp121Ala Uncertain significance ★ ⚠ same residue
NBN p.Asp121= Likely benign ★ same residue
NBN c.1124+1G>C Likely pathogenic ★★ same condition
NBN c.1124+2T>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-asp121val (accessed [today's date]).

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