Is NCSTN p.Phe677= (c.2031C>T) pathogenic?

NCSTN p.Phe677= (c.2031C>T) is classified Likely benign in NCSTN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-20). Ultra-rare (popmax 0.0283%, amr); Associated with Inborn genetic diseases.

What condition is associated with NCSTN p.Phe677= (c.2031C>T)?

NCSTN p.Phe677= (c.2031C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NCSTN p.Phe677= (c.2031C>T) in the general population?

NCSTN p.Phe677= (c.2031C>T) is ultra-rare (popmax 0.0283%, amr) (gnomAD).

NCSTN p.Phe677=

c.2031C>T · rs201068213 · VCV1643865

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0283%, amr)

Conditions

Inborn genetic diseases

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 -1.1	GERP -3.7, phastCons 0.001
Overall
CADD	10.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0283% Admixed American · 17/60,006 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0013% 21/1,614,042 alleles · ultra-rare exomes 20/1,461,886 · genomes 1/152,156 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0283%	3,530
Remaining individualsnot grpmax-eligible	0.0032%	31,243
South Asian	0.0022%	45,541

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.Phe677=
Coding: c.2031C>T
MANE Select: NM_015331
dbSNP: rs201068213
Type: single nucleotide variant
Location: chr1:160358172 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.73 · 30 PDB
Residue 677: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NCSTN p.Ala207Pro Uncertain significance ★★ ⚠ same condition
NCSTN p.Ala298Thr Uncertain significance ★★ ⚠ same condition
NCSTN p.Ala484Thr Uncertain significance ★★ same condition
NCSTN p.Ala48Ser Uncertain significance ★★ ⚠ same condition
NCSTN p.Ala497Val Uncertain significance ★★ ⚠ same condition
NCSTN p.Ala664Gly Uncertain significance ★★ same condition
NCSTN p.Ala664Thr Uncertain significance ★★ same condition
NCSTN p.Arg105Trp 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/ncstn-p-phe677 (accessed [today's date]).

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