Is NRAP p.Pro977Arg (c.2930C>G) pathogenic?

NRAP p.Pro977Arg (c.2930C>G) is classified Uncertain significance in NRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.8299); Very rare (popmax 0.00221%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NRAP p.Pro977Arg (c.2930C>G)?

NRAP p.Pro977Arg (c.2930C>G) is associated with Inborn genetic diseases (ClinVar).

How common is NRAP p.Pro977Arg (c.2930C>G) in the general population?

NRAP p.Pro977Arg (c.2930C>G) is very rare (popmax 0.00221%, nfe) (gnomAD).

What do computational predictors say about NRAP p.Pro977Arg (c.2930C>G)?

AlphaMissense predicts likely pathogenic (score 0.8299) — an in-silico prediction, not a clinical call.

NRAP p.Pro977Arg

c.2930C>G · rs763330113 · VCV2218505

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8299 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8299	likely pathogenic · top 6% in NRAP
REVEL	0.481	indeterminate
SaProt	LLR -12.68	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.8, phastCons 1
Overall
CADD	26.1	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

Grpmax group 0.00221% European (non-Finnish) · 26/1,178,548 alleles

Filtering AF 0.00154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00174% 28/1,612,264 alleles · very rare exomes 26/1,460,224 · genomes 2/152,040 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00221%	45,329
Admixed American	0.00167%	59,976
Remaining individualsnot grpmax-eligible	0.0016%	62,420

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: NRAP
Protein: p.Pro977Arg
Coding: c.2930C>G
MANE Select: NM_198060
dbSNP: rs763330113
Type: single nucleotide variant
Location: chr10:113617498 (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.Pro977Leu Uncertain significance ★★ same residue
NRAP p.Pro977Ser Uncertain significance ★ ⚠ 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

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-pro977arg (accessed [today's date]).

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