Is NRAP p.Pro391Ser (c.1171C>T) pathogenic?

NRAP p.Pro391Ser (c.1171C>T) is classified Uncertain significance in NRAP (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-25). AlphaMissense: likely pathogenic (0.6019); Very rare (popmax 0.00892%, eas).

How common is NRAP p.Pro391Ser (c.1171C>T) in the general population?

NRAP p.Pro391Ser (c.1171C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about NRAP p.Pro391Ser (c.1171C>T)?

AlphaMissense predicts likely pathogenic (score 0.6019) — an in-silico prediction, not a clinical call.

NRAP p.Pro391Ser

c.1171C>T · VCV3344492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6019	likely pathogenic
REVEL	0.511	indeterminate
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,860 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00056% 9/1,608,526 alleles · very rare exomes 8/1,456,226 · genomes 1/152,300 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,215
South Asian	0.0044%	22,738
European (non-Finnish)	8.51e-05%	1,174,905

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.Pro391Ser
Coding: c.1171C>T
MANE Select: NM_198060
Type: single nucleotide variant
Location: chr10:113642978 (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

Similar variants

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NRAP p.Arg1330Gln Uncertain significance ★★ ⚠ same type
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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-pro391ser (accessed [today's date]).

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