Is TULP3 p.Arg291Gln (c.872G>A) pathogenic?

TULP3 p.Arg291Gln (c.872G>A) is classified Likely benign in TULP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.0723); Ultra-rare (popmax 0.0282%, afr); Associated with Inborn genetic diseases.

What condition is associated with TULP3 p.Arg291Gln (c.872G>A)?

TULP3 p.Arg291Gln (c.872G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TULP3 p.Arg291Gln (c.872G>A) in the general population?

TULP3 p.Arg291Gln (c.872G>A) is ultra-rare (popmax 0.0282%, afr) (gnomAD).

What do computational predictors say about TULP3 p.Arg291Gln (c.872G>A)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

TULP3 p.Arg291Gln

c.872G>A · VCV4633973

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0282%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -6.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP -1.3, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 48 kb · p 0.45 · regional, not allelic
Overall
CADD	7.248	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 0.0282% African / African-American · 21/74,390 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0158%

Overall 0.00162% 26/1,604,992 alleles · ultra-rare exomes 12/1,452,808 · genomes 14/152,184 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0282%	3,542
South Asian	0.00112%	89,410
European (non-Finnish)	0.00034%	294,037

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.Arg291Gln
Coding: c.872G>A
MANE Select: NM_003324
Type: single nucleotide variant
Location: chr12:2934509 (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.Arg291Trp Uncertain significance ★ ⚠ 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-arg291gln (accessed [today's date]).

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