Is TULP3 p.Val49Ala (c.146T>C) pathogenic?

TULP3 p.Val49Ala (c.146T>C) is classified Uncertain significance in TULP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: ambiguous (0.5048); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with TULP3 p.Val49Ala (c.146T>C)?

TULP3 p.Val49Ala (c.146T>C) is associated with Inborn genetic diseases (ClinVar).

How common is TULP3 p.Val49Ala (c.146T>C) in the general population?

TULP3 p.Val49Ala (c.146T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about TULP3 p.Val49Ala (c.146T>C)?

AlphaMissense predicts ambiguous (score 0.5048) — an in-silico prediction, not a clinical call.

TULP3 p.Val49Ala

c.146T>C · rs1269807743 · VCV2241221

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5048 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5048	ambiguous
REVEL	0.776	moderately pathogenic-leaning
SaProt	LLR -6.34	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 48 kb · p 0.45 · regional, not allelic
Overall
CADD	22.6	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 0.0011% South Asian · 1/91,082 alleles

Overall 0.000124% 2/1,614,114 alleles · very rare exomes 2/1,461,892 · genomes 0/152,222 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,082
European (non-Finnish)	8.47e-05%	1,180,034

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.Val49Ala
Coding: c.146T>C
MANE Select: NM_003324
dbSNP: rs1269807743
Type: single nucleotide variant
Location: chr12:2920815 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.51 · 1 PDB
Residue 49: the 'required for association with the ift complex a (ift-a)' 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-val49ala (accessed [today's date]).

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