Is NDP p.Val5= (c.15A>G) pathogenic?

NDP p.Val5= (c.15A>G) is classified Likely benign in NDP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-27). Very rare (popmax 0.00156%, nfe).

How common is NDP p.Val5= (c.15A>G) in the general population?

NDP p.Val5= (c.15A>G) is very rare (popmax 0.00156%, nfe) (gnomAD).

NDP p.Val5=

c.15A>G · rs1396654531 · VCV707005

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00156%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.3	GERP 0.49, phastCons 1
Overall
CADD	9.893	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00156% European (non-Finnish) · 14/894,807 alleles

Filtering AF 0.000908% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00071%

Overall 0.00124% 15/1,209,904 alleles · very rare exomes 14/1,097,547 · genomes 1/112,357 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0021%	47,581
European (non-Finnish)grpmax	0.00156%	63,915

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val5=
Coding: c.15A>G
MANE Select: NM_000266
dbSNP: rs1396654531
Type: single nucleotide variant
Location: chrX:43958631 (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.Val5Ala Uncertain significance ★ ⚠ same residue
NDP p.Val5Ile 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-val5 (accessed [today's date]).

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