Is TULP1 p.Arg9Gln (c.26G>A) pathogenic?

TULP1 p.Arg9Gln (c.26G>A) is classified Uncertain significance in TULP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-12). AlphaMissense: likely benign (0.118); Very rare (popmax 0.00135%, afr); Associated with retinitis pigmentosa.

What condition is associated with TULP1 p.Arg9Gln (c.26G>A)?

TULP1 p.Arg9Gln (c.26G>A) is associated with retinitis pigmentosa, Leber congenital amaurosis 15 (ClinVar).

How common is TULP1 p.Arg9Gln (c.26G>A) in the general population?

TULP1 p.Arg9Gln (c.26G>A) is very rare (popmax 0.00135%, afr) (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.Arg9Gln (c.26G>A)?

AlphaMissense predicts likely benign (score 0.118) — an in-silico prediction, not a clinical call.

TULP1 p.Arg9Gln

c.26G>A · rs886061338 · VCV356477

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.118 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.118	likely benign
REVEL	0.371	indeterminate
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3	GERP 0.98, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 3,598 bp · p 0.36 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 0.00135% African / African-American · 1/73,976 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000249% 4/1,608,110 alleles · very rare exomes 4/1,457,098 · genomes 0/151,012 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,158
African / African-Americangrpmax	0.00135%	73,976
European (non-Finnish)	0.00017%	588,699

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg9Gln
Coding: c.26G>A
MANE Select: NM_003322
dbSNP: rs886061338
Type: single nucleotide variant
Location: chr6:35512833 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 9: the 'disordered' region

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

Also linked: Leber congenital amaurosis 15

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.Arg9Ter Pathogenic/Likely pathogenic ★★ same residue
TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.99+1G>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg311Gln Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg311Trp Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg342Ter Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg34Ter 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-arg9gln (accessed [today's date]).

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