Is NBN p.Ala481= (c.1443A>C) pathogenic?

NBN p.Ala481= (c.1443A>C) is classified Likely benign in NBN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-31). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with NBN p.Ala481= (c.1443A>C)?

NBN p.Ala481= (c.1443A>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is NBN p.Ala481= (c.1443A>C) in the general population?

NBN p.Ala481= (c.1443A>C) is absent from gnomAD v4.1 (gnomAD).

NBN p.Ala481=

c.1443A>C · rs751121403 · VCV1772737

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP 1.8, phastCons 1
Overall
CADD	10.81	PHRED · no single calibrated threshold — expert panels disagree

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.Ala481=
Coding: c.1443A>C
MANE Select: NM_002485
dbSNP: rs751121403
Type: single nucleotide variant
Location: chr8:89953646 (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

Similar variants

NBN p.Ala481Pro Uncertain significance ★★ ⚠ same residue
NBN p.Ala481Thr Uncertain significance ★ ⚠ same residue
NBN p.Ala481Val Uncertain significance ★★ ⚠ same residue
NBN c.1124+1G>C Likely pathogenic ★★ same condition
NBN c.171+1G>A Likely pathogenic ★★ same condition
NBN c.172-2A>G Likely pathogenic ★★ same condition
NBN c.1845+1G>A Likely pathogenic ★★ same condition
NBN c.2070+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-ala481 (accessed [today's date]).

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