Is NRAP p.Tyr1237His (c.3709T>C) pathogenic?

NRAP p.Tyr1237His (c.3709T>C) is classified Uncertain significance in NRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.6605); No allele count reported in gnomAD v4.1 (AN 1,610,006); Associated with Inborn genetic diseases.

What condition is associated with NRAP p.Tyr1237His (c.3709T>C)?

NRAP p.Tyr1237His (c.3709T>C) is associated with Inborn genetic diseases (ClinVar).

How common is NRAP p.Tyr1237His (c.3709T>C) in the general population?

NRAP p.Tyr1237His (c.3709T>C) is no allele count reported in gnomAD v4.1 (AN 1,610,006) (gnomAD).

What do computational predictors say about NRAP p.Tyr1237His (c.3709T>C)?

AlphaMissense predicts likely pathogenic (score 0.6605) — an in-silico prediction, not a clinical call.

NRAP p.Tyr1237His

c.3709T>C · VCV4626430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6605 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,610,006)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6605	likely pathogenic
REVEL	0.95	strongly pathogenic-leaning
SaProt	LLR -10.86	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 11	GERP 2.6, phastCons 1
Overall
CADD	26.7	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

No allele count reported in gnomAD v4.1 (AN 1,610,006). 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.Tyr1237His
Coding: c.3709T>C
MANE Select: NM_198060
Type: single nucleotide variant
Location: chr10:113606276 (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.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
NRAP p.Lys794Gln 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-tyr1237his (accessed [today's date]).

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