Is NBN p.Ser72Thr (c.214T>A) pathogenic?

NBN p.Ser72Thr (c.214T>A) is classified Uncertain significance in NBN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-17). AlphaMissense: likely pathogenic (0.7233); Absent from gnomAD v4.1.

How common is NBN p.Ser72Thr (c.214T>A) in the general population?

NBN p.Ser72Thr (c.214T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NBN p.Ser72Thr (c.214T>A)?

AlphaMissense predicts likely pathogenic (score 0.7233) — an in-silico prediction, not a clinical call.

NBN p.Ser72Thr

c.214T>A · VCV3769784

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7233 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7233	likely pathogenic
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -11.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Ser72Thr
Coding: c.214T>A
MANE Select: NM_057091 · reported on NM_002485
Type: single nucleotide variant
Location: chr8:89981481 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB
Residue 72: the 'disordered' region

Full NBN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NBN p.Ser72Phe Uncertain significance ★★ ⚠ same residue
ARTN p.Arg72His Uncertain significance ★ ⚠ same residue
NBN p.Ser72= Likely benign ★ same residue
NBN p.Ser72fs Likely pathogenic ★ same residue
NBN p.Ser72del Uncertain significance ★ same residue
NBN p.Ser72delinsTrpAsnArgSerGlyGlnPro Uncertain significance same residue
NBN c.1124+1G>C Likely pathogenic ★★ same type
NBN c.1124+2T>G Likely pathogenic ★★ same type

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-ser72thr (accessed [today's date]).

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