Is TULP1 p.Glu433Lys (c.1297G>A) pathogenic?

TULP1 p.Glu433Lys (c.1297G>A) is classified Conflicting classifications of pathogenicity in TULP1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.1025); Rare (popmax 0.458%, afr); Associated with inherited retinal dystrophy.

What condition is associated with TULP1 p.Glu433Lys (c.1297G>A)?

TULP1 p.Glu433Lys (c.1297G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is TULP1 p.Glu433Lys (c.1297G>A) in the general population?

TULP1 p.Glu433Lys (c.1297G>A) is rare (popmax 0.458%, afr) (gnomAD).

What do computational predictors say about TULP1 p.Glu433Lys (c.1297G>A)?

AlphaMissense predicts likely benign (score 0.1025) — an in-silico prediction, not a clinical call.

TULP1 p.Glu433Lys

c.1297G>A · rs74461100 · VCV770046

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1025 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.458%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1025	likely benign
REVEL	0.446	indeterminate
SaProt	LLR -10.64	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP -0.25, phastCons 0.2
Regional constraint	o/e 1.02	unconstrained · MANE · 7,948 bp · p 0.64 · regional, not allelic
Overall
CADD	19.66	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 0.458% African / African-American · 341/74,414 alleles

Filtering AF 0.418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.402%

Overall 0.0276% 437/1,586,182 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.458%	218
Middle Eastern	0.0663%	1,509
Remaining individualsnot grpmax-eligible	0.0521%	1,919
Admixed American	0.0462%	2,163
South Asian	0.00577%	17,332
European (non-Finnish)	0.00249%	40,219

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.Glu433Lys
Coding: c.1297G>A
MANE Select: NM_003322
dbSNP: rs74461100
Type: single nucleotide variant
Location: chr6:35503585 (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

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TULP1 p.Glu433Ter Pathogenic ★ same residue
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.718+2T>C Pathogenic ★★ same condition
TULP1 p.Arg361Ter Pathogenic ★★ same condition
TULP1 p.Arg400Trp Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg419Trp Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg440Ter Pathogenic ★★ same condition
TULP1 p.Asn349Lys 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-glu433lys (accessed [today's date]).

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