Is NCDN p.Val362= (c.1086G>A) pathogenic?

NCDN p.Val362= (c.1086G>A) is classified Likely benign in NCDN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). Very rare (popmax 0.00167%, amr).

How common is NCDN p.Val362= (c.1086G>A) in the general population?

NCDN p.Val362= (c.1086G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

NCDN p.Val362=

c.1086G>A · rs1335269993 · VCV3251103

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.44	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.053	GERP -4.4, phastCons 0.56
Overall
CADD	12.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,800 alleles

Overall 0.00031% 5/1,611,454 alleles · very rare exomes 5/1,459,146 · genomes 0/152,308 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00478%	20,933
Admixed Americangrpmax	0.00167%	59,800
European (non-Finnish)	8.48e-05%	1,179,446

Finnish 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: NCDN
Protein: p.Val362=
Coding: c.1086G>A
MANE Select: NM_014284
dbSNP: rs1335269993
Type: single nucleotide variant
Location: chr1:35561237 (GRCh38)
Gene constraint: LOEUF 0.261 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.12

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

Similar variants

NCDN p.Arg259Trp Uncertain significance ★★ ⚠ same type
NCDN p.Arg423His Uncertain significance ★★ ⚠ same type
NCDN p.Gly164Ser Uncertain significance ★★ ⚠ same type
NCDN p.Gly189Ser Uncertain significance ★★ ⚠ same type
NCDN p.Arg478Gln Pathogenic ★ ⚠ same type
NCDN p.Glu433Gln Likely pathogenic ★ ⚠ same type
NCDN p.Pro533Leu Likely pathogenic ★ same type
NCDN p.Pro652Leu 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/ncdn-p-val362 (accessed [today's date]).

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