Is NRAP p.Ala82Asp (c.245C>A) pathogenic?

NRAP p.Ala82Asp (c.245C>A) is classified Uncertain significance in NRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.1124); Ultra-rare (popmax 0.1%, sas); Associated with Inborn genetic diseases.

What condition is associated with NRAP p.Ala82Asp (c.245C>A)?

NRAP p.Ala82Asp (c.245C>A) is associated with Inborn genetic diseases (ClinVar).

How common is NRAP p.Ala82Asp (c.245C>A) in the general population?

NRAP p.Ala82Asp (c.245C>A) is ultra-rare (popmax 0.1%, sas) (gnomAD).

What do computational predictors say about NRAP p.Ala82Asp (c.245C>A)?

AlphaMissense predicts likely benign (score 0.1124) — an in-silico prediction, not a clinical call.

NRAP p.Ala82Asp

c.245C>A · rs115585400 · VCV2407784

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1124 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.1%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1124	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -6.14	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 5.4	GERP 1.1, phastCons 1
Overall
CADD	19.01	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

Grpmax group 0.1% South Asian · 90/90,038 alleles

Filtering AF 0.0833% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.077%

Overall 0.00624% 97/1,555,102 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.1%	1,000
Remaining individualsnot grpmax-eligible	0.00826%	12,104
African / African-American	0.00136%	73,670
European (non-Finnish)	8.88e-05%	1,126,340

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.Ala82Asp
Coding: c.245C>A
MANE Select: NM_198060
dbSNP: rs115585400
Type: single nucleotide variant
Location: chr10:113662689 (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.Ala82Val Benign/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-ala82asp (accessed [today's date]).

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