Is NANS p.Asp34= (c.102C>T) pathogenic?

NANS p.Asp34= (c.102C>T) is classified Benign in NANS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Common (popmax 62.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with spondyloepimetaphyseal dysplasia, Genevieve type.

What condition is associated with NANS p.Asp34= (c.102C>T)?

NANS p.Asp34= (c.102C>T) is associated with spondyloepimetaphyseal dysplasia, Genevieve type (ClinVar).

NANS p.Asp34=

Q: How common is NANS p.Asp34= (c.102C>T) in the general population?

NANS p.Asp34= (c.102C>T) is common (popmax 62.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Spondyloepimetaphyseal dysplasia, Geneviève type inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.102C>T · rs3739670 · VCV1241755

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 62.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

spondyloepimetaphyseal dysplasia, Genevieve type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -4
Overall
CADD	8.038	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 62.8% African / African-American · 46,607/74,208 alleles

Filtering AF 62.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 62.1%

Overall 23.8% 382,699/1,608,508 alleles · common exomes 333,033/1,456,368 · genomes 49,666/152,140 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	62.8%	2
South Asian	48.8%	2
Middle Eastern	37.5%	3
Remaining individualsnot grpmax-eligible	25.2%	4
Admixed American	23.8%	4
Ashkenazi Jewishnot grpmax-eligible	22.7%	4
Finnishnot grpmax-eligible	20.6%	5
European (non-Finnish)	20%	5
Amishnot grpmax-eligible	10.7%	9
East Asian	9.9%	10

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: NANS
Protein: p.Asp34=
Coding: c.102C>T
MANE Select: NM_018946
dbSNP: rs3739670
Type: single nucleotide variant
Location: chr9:98056910 (GRCh38)
Gene constraint: LOEUF 1.053 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.04 · 1 PDB

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

Disease context

spondyloepimetaphyseal dysplasia, Genevieve type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spondyloepimetaphyseal dysplasia, Geneviève type (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

NANS c.448+1G>A Pathogenic/Likely pathogenic ★★ same condition
NANS p.Glu258Ter Pathogenic/Likely pathogenic ★★ same condition
NANS p.Pro18Ala Uncertain significance ★★ ⚠ same condition
NANS p.Ala51= Benign ★★ same condition
NANS p.Met1Val Likely pathogenic ★ same condition
NANS p.Trp245Ter Likely pathogenic ★ same condition
NANS p.Arg237Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
NANS p.Ile223Thr 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/nans-p-asp34 (accessed [today's date]).

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