Is NBN p.Ser615Phe (c.1844C>T) pathogenic?

NBN p.Ser615Phe (c.1844C>T) is classified Uncertain significance in NBN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-05-20). AlphaMissense: likely benign (0.0925); Absent from gnomAD v4.1; Associated with aplastic anemia.

What condition is associated with NBN p.Ser615Phe (c.1844C>T)?

NBN p.Ser615Phe (c.1844C>T) is associated with aplastic anemia, Nijmegen breakage syndrome, hereditary neoplastic syndrome (ClinVar).

How common is NBN p.Ser615Phe (c.1844C>T) in the general population?

NBN p.Ser615Phe (c.1844C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NBN p.Ser615Phe (c.1844C>T)?

AlphaMissense predicts likely benign (score 0.0925) — an in-silico prediction, not a clinical call.

NBN p.Ser615Phe

c.1844C>T · rs1810520002 · VCV837776

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0925 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

aplastic anemia

Computational evidence

Protein change
AlphaMissense	0.0925	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 1.8, phastCons 1
Overall
CADD	17.18	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Ser615Phe
Coding: c.1844C>T
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs1810520002
Type: single nucleotide variant
Location: chr8:89953245 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB

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

Disease context

aplastic anemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Nijmegen breakage syndrome hereditary neoplastic syndrome

Similar variants

NBN p.Ser615Cys Uncertain significance ★★ ⚠ same residue
NBN p.Ser615= Conflicting classifications of pathogenicity ★ same residue
NBN p.Ser615Pro Conflicting classifications of pathogenicity ★ ⚠ 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

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-ser615phe (accessed [today's date]).

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