Is NRAP p.Ser782Arg (c.2346C>A) pathogenic?

NRAP p.Ser782Arg (c.2346C>A) is classified Uncertain significance in NRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely pathogenic (0.9715); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NRAP p.Ser782Arg (c.2346C>A)?

NRAP p.Ser782Arg (c.2346C>A) is associated with Inborn genetic diseases (ClinVar).

How common is NRAP p.Ser782Arg (c.2346C>A) in the general population?

NRAP p.Ser782Arg (c.2346C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NRAP p.Ser782Arg (c.2346C>A)?

AlphaMissense predicts likely pathogenic (score 0.9715) — an in-silico prediction, not a clinical call.

NRAP p.Ser782Arg

c.2346C>A · VCV4122609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9715 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9715	likely pathogenic · top 1% in NRAP
REVEL	0.663	pathogenic-leaning
SaProt	LLR -13.90	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.5	GERP -4.2
Overall
CADD	3.412	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: NRAP
Protein: p.Ser782Arg
Coding: c.2346C>A
MANE Select: NM_198060
Type: single nucleotide variant
Location: chr10:113624829 (GRCh38)
Gene constraint: LOEUF 1.045 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.98

Full NRAP 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

NRAP p.Ser782= Likely benign ★ same residue
NRAP p.Ala571Thr Uncertain significance ★★ same condition
NRAP p.Arg1559Gln Uncertain significance ★★ ⚠ same condition
NRAP p.Asp633Tyr Uncertain significance ★★ ⚠ same condition
NRAP p.Gly277Val Uncertain significance ★★ ⚠ same condition
NRAP p.His1003Tyr Uncertain significance ★★ ⚠ same condition
NRAP p.His639Arg Uncertain significance ★★ ⚠ same condition
NRAP p.Lys1590Arg 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/nrap-p-ser782arg (accessed [today's date]).

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