Is TULP1 p.Ser75Phe (c.224C>T) pathogenic?

TULP1 p.Ser75Phe (c.224C>T) is classified Uncertain significance in TULP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-20). AlphaMissense: likely benign (0.1068); Ultra-rare (popmax 0.017%, mid); Associated with retinitis pigmentosa.

What condition is associated with TULP1 p.Ser75Phe (c.224C>T)?

TULP1 p.Ser75Phe (c.224C>T) is associated with retinitis pigmentosa, Leber congenital amaurosis 15 (ClinVar).

How common is TULP1 p.Ser75Phe (c.224C>T) in the general population?

TULP1 p.Ser75Phe (c.224C>T) is ultra-rare (popmax 0.017%, mid) (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.Ser75Phe (c.224C>T)?

AlphaMissense predicts likely benign (score 0.1068) — an in-silico prediction, not a clinical call.

TULP1 p.Ser75Phe

c.224C>T · rs1244588827 · VCV905305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1068 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.1068	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -9.43	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 -0.071	GERP 0.086
Regional constraint	o/e 1.05	unconstrained · MANE · 3,598 bp · p 0.36 · regional, not allelic
Overall
CADD	18.93	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 0.017% Middle Eastern · 1/5,876 alleles

Overall 0.00019% 3/1,576,516 alleles · ultra-rare exomes 3/1,424,346 · genomes 0/152,170 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.017%	5,876
East Asian	0.00234%	42,780
South Asian	0.00116%	86,294

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.Ser75Phe
Coding: c.224C>T
MANE Select: NM_003322
dbSNP: rs1244588827
Type: single nucleotide variant
Location: chr6:35511773 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 75: 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.Ser75= Likely benign ★ 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-ser75phe (accessed [today's date]).

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