Is TULP3 p.Thr276Ser (c.827C>G) pathogenic?

TULP3 p.Thr276Ser (c.827C>G) is classified Uncertain significance in TULP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-10). AlphaMissense: likely pathogenic (0.7258); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TULP3 p.Thr276Ser (c.827C>G)?

TULP3 p.Thr276Ser (c.827C>G) is associated with Inborn genetic diseases (ClinVar).

How common is TULP3 p.Thr276Ser (c.827C>G) in the general population?

TULP3 p.Thr276Ser (c.827C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TULP3 p.Thr276Ser (c.827C>G)?

AlphaMissense predicts likely pathogenic (score 0.7258) — an in-silico prediction, not a clinical call.

TULP3 p.Thr276Ser

c.827C>G · VCV3464475

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7258 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7258	likely pathogenic
REVEL	0.861	moderately pathogenic-leaning
SaProt	LLR -9.09	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 48 kb · p 0.45 · regional, not allelic
Overall
CADD	24.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TULP3
Protein: p.Thr276Ser
Coding: c.827C>G
MANE Select: NM_003324
Type: single nucleotide variant
Location: chr12:2934464 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.51 · 1 PDB
Residue 276: 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-thr276ser (accessed [today's date]).

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