Is NCDN p.Val80= (c.240C>T) pathogenic?

NCDN p.Val80= (c.240C>T) is classified Likely benign in NCDN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). Rare (popmax 0.139%, afr).

How common is NCDN p.Val80= (c.240C>T) in the general population?

NCDN p.Val80= (c.240C>T) is rare (popmax 0.139%, afr) (gnomAD).

NCDN p.Val80=

c.240C>T · rs146042879 · VCV1694506

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.139%, afr)

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 -1.8	GERP -3.8
Overall
CADD	3.288	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.139% African / African-American · 104/75,050 alleles

Filtering AF 0.117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.109%

Overall 0.00793% 128/1,614,002 alleles · rare exomes 63/1,461,668 · genomes 65/152,334 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.139%	722
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.01%	10,004
European (non-Finnish)	0.000847%	118,004

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.Val80=
Coding: c.240C>T
MANE Select: NM_014284
dbSNP: rs146042879
Type: single nucleotide variant
Location: chr1:35560391 (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.Val80Leu Uncertain significance ★ ⚠ same residue
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

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-val80 (accessed [today's date]).

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