Is NCSTN p.Pro468= (c.1404C>T) pathogenic?

NCSTN p.Pro468= (c.1404C>T) is classified Likely benign in NCSTN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-28). Very rare (popmax 0.00266%, afr).

How common is NCSTN p.Pro468= (c.1404C>T) in the general population?

NCSTN p.Pro468= (c.1404C>T) is very rare (popmax 0.00266%, afr) (gnomAD).

NCSTN p.Pro468=

c.1404C>T · rs200322980 · VCV1630862

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00266%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.128	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.6	GERP -4
Overall
CADD	1.012	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00266% African / African-American · 2/75,054 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,614,200 alleles · very rare exomes 5/1,461,874 · genomes 3/152,326 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00266%	37,527
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000424%	236,005

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.Pro468=
Coding: c.1404C>T
MANE Select: NM_015331
dbSNP: rs200322980
Type: single nucleotide variant
Location: chr1:160355706 (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.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
NCSTN p.Arg105Trp 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-pro468 (accessed [today's date]).

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