Is NUS1 p.Pro98Ser (c.292C>T) pathogenic?

NUS1 p.Pro98Ser (c.292C>T) is classified Uncertain significance in NUS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: likely pathogenic (0.9848); No allele count reported in gnomAD v4.1 (AN 1,548,490); Associated with Inborn genetic diseases.

What condition is associated with NUS1 p.Pro98Ser (c.292C>T)?

NUS1 p.Pro98Ser (c.292C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NUS1 p.Pro98Ser (c.292C>T) in the general population?

NUS1 p.Pro98Ser (c.292C>T) is no allele count reported in gnomAD v4.1 (AN 1,548,490) (gnomAD).

What do computational predictors say about NUS1 p.Pro98Ser (c.292C>T)?

AlphaMissense predicts likely pathogenic (score 0.9848) — an in-silico prediction, not a clinical call.

NUS1 p.Pro98Ser

c.292C>T · VCV3881945

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9848 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,548,490)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9848	likely pathogenic · top 1% in NUS1
REVEL	0.612	indeterminate
SaProt	LLR -13.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 3.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 18 kb · p 0.003 · regional, not allelic
Overall
CADD	25.8	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

No allele count reported in gnomAD v4.1 (AN 1,548,490). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NUS1
Protein: p.Pro98Ser
Coding: c.292C>T
MANE Select: NM_138459
Type: single nucleotide variant
Location: chr6:117675962 (GRCh38)
Gene constraint: LOEUF 0.182 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.01 · 9 PDB

Full NUS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NUS1 p.Pro98Arg Uncertain significance ★ ⚠ same residue
NUS1 p.Ala187Val Uncertain significance ★★ ⚠ same condition
NUS1 p.Arg10Trp Uncertain significance ★★ ⚠ same condition
NUS1 p.Arg57Cys Uncertain significance ★★ ⚠ same condition
NUS1 p.Asn175Asp Uncertain significance ★★ ⚠ same condition
NUS1 p.Gln157Arg Uncertain significance ★★ ⚠ same condition
NUS1 p.Gln180Glu Uncertain significance ★★ ⚠ same condition
NUS1 p.Glu6Gln Uncertain significance ★★ ⚠ 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/nus1-p-pro98ser (accessed [today's date]).

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