Is TULP3 p.Val107Ile (c.319G>A) pathogenic?

TULP3 p.Val107Ile (c.319G>A) is classified Uncertain significance in TULP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). AlphaMissense: likely benign (0.0688); Rare (popmax 0.251%, afr); Associated with Inborn genetic diseases.

What condition is associated with TULP3 p.Val107Ile (c.319G>A)?

TULP3 p.Val107Ile (c.319G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TULP3 p.Val107Ile (c.319G>A) in the general population?

TULP3 p.Val107Ile (c.319G>A) is rare (popmax 0.251%, afr) (gnomAD).

What do computational predictors say about TULP3 p.Val107Ile (c.319G>A)?

AlphaMissense predicts likely benign (score 0.0688) — an in-silico prediction, not a clinical call.

TULP3 p.Val107Ile

c.319G>A · rs142250486 · VCV3184873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0688 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.251%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0688	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -6.78	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 2.3	GERP -0.57, phastCons 0.21
Regional constraint	o/e 0.97	unconstrained · MANE · 48 kb · p 0.45 · regional, not allelic
Overall
CADD	7.747	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 0.251% African / African-American · 188/75,050 alleles

Filtering AF 0.221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.21%

Overall 0.0153% 247/1,614,154 alleles · rare exomes 108/1,461,860 · genomes 139/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.251%	399
Admixed American	0.0567%	1,765
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0288%	3,473
European (non-Finnish)	0.000339%	295,008

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.Val107Ile
Coding: c.319G>A
MANE Select: NM_003324
dbSNP: rs142250486
Type: single nucleotide variant
Location: chr12:2922327 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.51 · 1 PDB
Residue 107: the 'disordered' region; 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.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
TULP3 c.*1136C>T Uncertain significance ★ same condition
TULP3 c.*1213G>C 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-val107ile (accessed [today's date]).

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