Is TULP1 p.Arg103Trp (c.307C>T) pathogenic?

TULP1 p.Arg103Trp (c.307C>T) is classified Uncertain significance in TULP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.1811); Very rare (popmax 0.00672%, afr); Associated with Inborn genetic diseases.

What condition is associated with TULP1 p.Arg103Trp (c.307C>T)?

TULP1 p.Arg103Trp (c.307C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TULP1 p.Arg103Trp (c.307C>T) in the general population?

TULP1 p.Arg103Trp (c.307C>T) is very rare (popmax 0.00672%, afr) (gnomAD).

What do computational predictors say about TULP1 p.Arg103Trp (c.307C>T)?

AlphaMissense predicts likely benign (score 0.1811) — an in-silico prediction, not a clinical call.

TULP1 p.Arg103Trp

c.307C>T · VCV4633970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1811 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00672%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1811	likely benign
REVEL	0.418	indeterminate
SaProt	LLR -7.59	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.55, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 3,598 bp · p 0.36 · regional, not allelic
Overall
CADD	26.0	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 0.00672% African / African-American · 5/74,428 alleles

Filtering AF 0.00256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000439% 7/1,594,638 alleles · very rare exomes 1/1,442,638 · genomes 6/152,000 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00672%	14,886
South Asian	0.00228%	43,826

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.Arg103Trp
Coding: c.307C>T
MANE Select: NM_003322
Type: single nucleotide variant
Location: chr6:35511690 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 103: the 'disordered' region

Full TULP1 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

TULP1 p.Ala221Val Uncertain significance ★★ ⚠ same condition
TULP1 p.Ala496Val Uncertain significance ★★ ⚠ same condition
TULP1 p.Ala524Thr Uncertain significance ★★ ⚠ same condition
TULP1 p.Ala531Thr Uncertain significance ★★ ⚠ same condition
TULP1 p.Arg159Ser Uncertain significance ★★ ⚠ same condition
TULP1 p.Arg308Gln Uncertain significance ★★ ⚠ same condition
TULP1 p.Arg344Gln Uncertain significance ★★ ⚠ same condition
TULP1 p.Arg416His 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/tulp1-p-arg103trp (accessed [today's date]).

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