Is TULP1 p.Arg420Pro (c.1259G>C) pathogenic?

TULP1 p.Arg420Pro (c.1259G>C) is classified Pathogenic in TULP1 (ClinVar, Single submitter, 3 submitters; last evaluated 2022-11-29). AlphaMissense: likely pathogenic (0.9713); Very rare (popmax 0.000256%, nfe); Associated with retinitis pigmentosa 14.

What condition is associated with TULP1 p.Arg420Pro (c.1259G>C)?

TULP1 p.Arg420Pro (c.1259G>C) is associated with retinitis pigmentosa 14 (ClinVar).

How common is TULP1 p.Arg420Pro (c.1259G>C) in the general population?

TULP1 p.Arg420Pro (c.1259G>C) is very rare (popmax 0.000256%, nfe) (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.Arg420Pro (c.1259G>C)?

AlphaMissense predicts likely pathogenic (score 0.9713) — an in-silico prediction, not a clinical call.

TULP1 p.Arg420Pro

c.1259G>C · rs121909073 · VCV7357

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9713 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000256%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 14

Computational evidence

Protein change
AlphaMissense	0.9713	likely pathogenic ✓ concordant with ClinVar
REVEL	0.87	moderately pathogenic-leaning
SaProt	LLR -14.95	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 5.9	GERP -0.67, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 7,948 bp · p 0.64 · regional, not allelic
Overall
CADD	32.0	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 0.000256% European (non-Finnish) · 3/1,172,726 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000188% 3/1,598,500 alleles · very rare exomes 3/1,446,182 · genomes 0/152,318 · joint denominator

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: TULP1
Protein: p.Arg420Pro
Coding: c.1259G>C
MANE Select: NM_003322
dbSNP: rs121909073
Type: single nucleotide variant
Location: chr6:35503623 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 420: a UniProt-annotated variant site (in rp14; no effect on rpe phagocytosis)

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

Disease context

retinitis pigmentosa 14 — 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 p.Arg420Ser Pathogenic ★★ same residue
TULP1 p.Arg420His Uncertain significance ★★ ⚠ same residue
TULP1 p.Arg420Cys Likely pathogenic ★ same residue
TULP1 p.Arg420Leu Uncertain significance ★ ⚠ same residue
TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.718+2T>C Pathogenic ★★ same condition
TULP1 c.99+1G>A Pathogenic/Likely pathogenic ★★ 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-arg420pro (accessed [today's date]).

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