Is NCSTN p.Arg32= (c.96G>A) pathogenic?

NCSTN p.Arg32= (c.96G>A) is classified Likely benign in NCSTN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-16). Very rare (popmax 0.000169%, nfe).

How common is NCSTN p.Arg32= (c.96G>A) in the general population?

NCSTN p.Arg32= (c.96G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

NCSTN p.Arg32=

c.96G>A · rs1327797915 · VCV2998976

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 -0.46	GERP -2.6
Overall
CADD	8.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,948 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,010 alleles · very rare exomes 2/1,461,766 · genomes 0/152,244 · 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: NCSTN
Protein: p.Arg32=
Coding: c.96G>A
MANE Select: NM_015331
dbSNP: rs1327797915
Type: single nucleotide variant
Location: chr1:160344732 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.73 · 30 PDB

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

Similar variants

NCSTN p.Arg32Met Uncertain significance ★ ⚠ same residue
NCSTN p.Ala207Pro Uncertain significance ★★ ⚠ same type
NCSTN p.Ala298Thr Uncertain significance ★★ ⚠ same type
NCSTN p.Ala484Thr Uncertain significance ★★ same type
NCSTN p.Ala48Ser Uncertain significance ★★ ⚠ same type
NCSTN p.Ala497Val Uncertain significance ★★ ⚠ same type
NCSTN p.Ala664Gly Uncertain significance ★★ same type
NCSTN p.Ala664Thr Uncertain significance ★★ 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/ncstn-p-arg32 (accessed [today's date]).

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