Is NRDC p.Val1069Leu (c.3205G>C) pathogenic?

NRDC p.Val1069Leu (c.3205G>C) is classified Uncertain significance in NRDC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.1672); Absent from gnomAD v4.1.

How common is NRDC p.Val1069Leu (c.3205G>C) in the general population?

NRDC p.Val1069Leu (c.3205G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NRDC p.Val1069Leu (c.3205G>C)?

AlphaMissense predicts likely benign (score 0.1672) — an in-silico prediction, not a clinical call.

NRDC p.Val1069Leu

c.3205G>C · rs1678479864 · VCV2251138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1672 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1672	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 2,344 bp · p 0.63 · regional, not allelic
Overall
CADD	21.7	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: NRDC
Protein: p.Val1069Leu
Coding: c.3205G>C
MANE Select: NM_001101662
dbSNP: rs1678479864
Type: single nucleotide variant
Location: chr1:51789621 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 83.20

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

Similar variants

NRDC p.Thr59= Benign ★★ same type
NRDC c.1439+1G>A Uncertain significance ★ same type
NRDC p.Glu148Lys Uncertain significance ★ ⚠ same type
NRDC p.Gly838Ser Uncertain significance ★ ⚠ same type
NRDC p.Lys1023Arg Uncertain significance ★ ⚠ same type
NRDC p.Met299Thr Uncertain significance ★ ⚠ same type
NRDC p.Thr957Ala Uncertain significance ★ ⚠ same type
NRDC p.Leu532= Likely benign ★ 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/nrdc-p-val1069leu (accessed [today's date]).

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