Is NCDN p.Ala599Ser (c.1795G>T) pathogenic?

NCDN p.Ala599Ser (c.1795G>T) is classified Uncertain significance in NCDN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1438); Absent from gnomAD v4.1.

How common is NCDN p.Ala599Ser (c.1795G>T) in the general population?

NCDN p.Ala599Ser (c.1795G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NCDN p.Ala599Ser (c.1795G>T)?

AlphaMissense predicts likely benign (score 0.1438) — an in-silico prediction, not a clinical call.

NCDN p.Ala599Ser

c.1795G>T · VCV3917840

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1438 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1438	likely benign
REVEL	0.254	benign-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 3,059 bp · p 6.1e-21 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NCDN
Protein: p.Ala599Ser
Coding: c.1795G>T
MANE Select: NM_014284
Type: single nucleotide variant
Location: chr1:35565268 (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-ala599ser (accessed [today's date]).

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