Is TULP1 p.Arg297Pro (c.890G>C) pathogenic?

TULP1 p.Arg297Pro (c.890G>C) is classified Uncertain significance in TULP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-04-06). AlphaMissense: likely pathogenic (0.8115); Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with TULP1 p.Arg297Pro (c.890G>C)?

TULP1 p.Arg297Pro (c.890G>C) is associated with retinitis pigmentosa (ClinVar).

How common is TULP1 p.Arg297Pro (c.890G>C) in the general population?

TULP1 p.Arg297Pro (c.890G>C) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TULP1 p.Arg297Pro (c.890G>C)?

AlphaMissense predicts likely pathogenic (score 0.8115) — an in-silico prediction, not a clinical call.

TULP1 p.Arg297Pro

c.890G>C · rs777674253 · VCV1297126

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8115 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.8115	likely pathogenic
REVEL	0.533	indeterminate
SaProt	LLR -13.06	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.88	GERP -2.6
Regional constraint	o/e 1.02	unconstrained · MANE · 7,948 bp · p 0.64 · regional, not allelic
Overall
CADD	19.39	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TULP1
Protein: p.Arg297Pro
Coding: c.890G>C
MANE Select: NM_003322
dbSNP: rs777674253
Type: single nucleotide variant
Location: chr6:35506112 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB

Full TULP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Asn349Lys Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Gln163Ter Pathogenic ★★ same condition
TULP1 p.Gln80Ter Pathogenic ★★ same condition
TULP1 p.Phe382Ser Pathogenic ★★ same condition
TULP1 p.Val423Ala Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.1495+3G>A Uncertain significance ★★ same condition
TULP1 p.Ala216Val 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/tulp1-p-arg297pro (accessed [today's date]).

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