Is NDP p.Ser92Pro (c.274T>C) pathogenic?

NDP p.Ser92Pro (c.274T>C) is classified Uncertain significance in NDP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-28). AlphaMissense: ambiguous (0.3779); Absent from gnomAD v4.1.

How common is NDP p.Ser92Pro (c.274T>C) in the general population?

NDP p.Ser92Pro (c.274T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NDP p.Ser92Pro (c.274T>C)?

AlphaMissense predicts ambiguous (score 0.3779) — an in-silico prediction, not a clinical call.

NDP p.Ser92Pro

c.274T>C · rs772386222 · VCV2737215

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3779 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3779	ambiguous
REVEL	0.537	indeterminate
SaProt	LLR -13.45	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 8,843 bp · p 0.0055 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

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.Ser92Pro
Coding: c.274T>C
MANE Select: NM_000266
dbSNP: rs772386222
Type: single nucleotide variant
Location: chrX:43949927 (GRCh38)
Structure: AlphaFold pLDDT 83.92 · 12 PDB
Residue 92: 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.Ser92Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
NDP p.Ser92= Likely benign ★ same residue
NDP p.Ser92fs Pathogenic ★ 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

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-ser92pro (accessed [today's date]).

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