Is NDP p.Pro98Arg (c.293C>G) pathogenic?

NDP p.Pro98Arg (c.293C>G) is classified Uncertain significance in NDP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-07). AlphaMissense: likely pathogenic (0.9902); Absent from gnomAD v4.1.

How common is NDP p.Pro98Arg (c.293C>G) in the general population?

NDP p.Pro98Arg (c.293C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NDP p.Pro98Arg (c.293C>G)?

AlphaMissense predicts likely pathogenic (score 0.9902) — an in-silico prediction, not a clinical call.

NDP p.Pro98Arg

c.293C>G · rs2519314974 · VCV2138557

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9902 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9902	likely pathogenic
REVEL	0.553	indeterminate
SaProt	LLR -11.58	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 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 8,843 bp · p 0.0055 · regional, not allelic
Overall
CADD	27.6	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: NDP
Protein: p.Pro98Arg
Coding: c.293C>G
MANE Select: NM_000266
dbSNP: rs2519314974
Type: single nucleotide variant
Location: chrX:43949908 (GRCh38)
Structure: AlphaFold pLDDT 83.92 · 12 PDB
Residue 98: the ctck domain; a UniProt-annotated variant site (in nd); a β-strand

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

Similar variants

NDP p.Pro98Leu Likely pathogenic ★ same residue
NDP p.Pro98_Gln99insArgPro Uncertain significance ★ same residue
NDP p.Ala118Asp Pathogenic/Likely pathogenic ★★ same type
NDP p.Arg109Ter Pathogenic ★★ same type
NDP p.Arg115Ter Pathogenic ★★ same type
NDP p.Arg121Trp Pathogenic/Likely pathogenic ★★ same type
NDP p.Arg37Ter Pathogenic/Likely pathogenic ★★ same type
NDP p.Arg38Cys 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/ndp-p-pro98arg (accessed [today's date]).

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