Is NDP p.Ser28Arg (c.84C>G) pathogenic?

NDP p.Ser28Arg (c.84C>G) is classified Uncertain significance in NDP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-07). AlphaMissense: likely benign (0.1745); Ultra-rare (popmax 0.0152%, amr).

How common is NDP p.Ser28Arg (c.84C>G) in the general population?

NDP p.Ser28Arg (c.84C>G) is ultra-rare (popmax 0.0152%, amr) (gnomAD).

What do computational predictors say about NDP p.Ser28Arg (c.84C>G)?

AlphaMissense predicts likely benign (score 0.1745) — an in-silico prediction, not a clinical call.

NDP p.Ser28Arg

c.84C>G · rs747904096 · VCV1042715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1745 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0152%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1745	likely benign
REVEL	0.367	indeterminate
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP 0.81, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 8,843 bp · p 0.0055 · regional, not allelic
Overall
CADD	12.76	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

Grpmax group 0.0152% Admixed American · 7/46,097 alleles

Filtering AF 0.00709% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00504%

Overall 0.000578% 7/1,210,958 alleles · ultra-rare exomes 7/1,096,871 · genomes 0/114,087 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: NDP
Protein: p.Ser28Arg
Coding: c.84C>G
MANE Select: NM_000266
dbSNP: rs747904096
Type: single nucleotide variant
Location: chrX:43958562 (GRCh38)
Structure: AlphaFold pLDDT 83.92 · 12 PDB

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

Similar variants

NDP p.Ser28= Likely benign ★ 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
NDP p.Arg74Cys 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-ser28arg (accessed [today's date]).

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