Is TULP3 p.Arg291Trp (c.871C>T) pathogenic?

TULP3 p.Arg291Trp (c.871C>T) is classified Uncertain significance in TULP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.124); Ultra-rare (popmax 0.065%, amr); Associated with Inborn genetic diseases.

What condition is associated with TULP3 p.Arg291Trp (c.871C>T)?

TULP3 p.Arg291Trp (c.871C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TULP3 p.Arg291Trp (c.871C>T) in the general population?

TULP3 p.Arg291Trp (c.871C>T) is ultra-rare (popmax 0.065%, amr) (gnomAD).

What do computational predictors say about TULP3 p.Arg291Trp (c.871C>T)?

AlphaMissense predicts likely benign (score 0.124) — an in-silico prediction, not a clinical call.

TULP3 p.Arg291Trp

c.871C>T · rs757488213 · VCV2388378

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.124 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.065%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.124	likely benign
REVEL	0.461	indeterminate
SaProt	LLR -10.57	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.7	GERP 0.79, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 48 kb · p 0.45 · regional, not allelic
Overall
CADD	23.1	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 0.065% Admixed American · 38/58,480 alleles

Filtering AF 0.0486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.043%

Overall 0.00374% 60/1,604,848 alleles · ultra-rare exomes 53/1,452,576 · genomes 7/152,272 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.065%	1,539
African / African-American	0.00671%	14,898
East Asian	0.00455%	21,977
Remaining individualsnot grpmax-eligible	0.00322%	31,065
European (non-Finnish)	0.00111%	90,463

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: TULP3
Protein: p.Arg291Trp
Coding: c.871C>T
MANE Select: NM_003324
dbSNP: rs757488213
Type: single nucleotide variant
Location: chr12:2934508 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.51 · 1 PDB
Residue 291: a UniProt-annotated variant site (in hrcdf)

Full TULP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TULP3 p.Arg291Gly Uncertain significance ★ ⚠ same residue
TULP3 p.Arg291Gln Likely benign ★ same residue
TULP3 p.Glu45Asp Uncertain significance ★★ ⚠ same condition
TULP3 c.*1102G>C Uncertain significance ★ same condition
TULP3 c.*1105A>C Uncertain significance ★ same condition
TULP3 c.*1119G>C Uncertain significance ★ same condition
TULP3 c.*1131G>T Uncertain significance ★ same condition
TULP3 c.*1133C>G 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/tulp3-p-arg291trp (accessed [today's date]).

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