Is NRAP p.Pro473Ser (c.1417C>T) pathogenic?

NRAP p.Pro473Ser (c.1417C>T) is classified Uncertain significance in NRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-20). AlphaMissense: likely benign (0.2794); No allele count reported in gnomAD v4.1 (AN 1,590,642).

How common is NRAP p.Pro473Ser (c.1417C>T) in the general population?

NRAP p.Pro473Ser (c.1417C>T) is no allele count reported in gnomAD v4.1 (AN 1,590,642) (gnomAD).

What do computational predictors say about NRAP p.Pro473Ser (c.1417C>T)?

AlphaMissense predicts likely benign (score 0.2794) — an in-silico prediction, not a clinical call.

NRAP p.Pro473Ser

c.1417C>T · VCV4909688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2794 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,590,642)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2794	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -5.14	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 8.6	GERP 2.3, phastCons 1
Overall
CADD	26.5	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

No allele count reported in gnomAD v4.1 (AN 1,590,642). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NRAP
Protein: p.Pro473Ser
Coding: c.1417C>T
MANE Select: NM_198060
Type: single nucleotide variant
Location: chr10:113640238 (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

NRAP p.Arg1037Ter Pathogenic/Likely pathogenic ★★ same type
NRAP p.Trp1033Ter Pathogenic/Likely pathogenic ★★ same type
NRAP c.360+1G>A Uncertain significance ★★ same type
NRAP p.Ala29Gly Uncertain significance ★★ ⚠ same type
NRAP p.Ala571Thr Uncertain significance ★★ same type
NRAP p.Arg1330Gln Uncertain significance ★★ ⚠ same type
NRAP p.Arg1559Gln Uncertain significance ★★ ⚠ same type
NRAP p.Arg428Cys Uncertain significance ★★ ⚠ 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/nrap-p-pro473ser (accessed [today's date]).

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