Is TULP3 p.Ala386Val (c.1157C>T) pathogenic?

TULP3 p.Ala386Val (c.1157C>T) is classified Uncertain significance in TULP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). AlphaMissense: likely pathogenic (0.9663); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with TULP3 p.Ala386Val (c.1157C>T)?

TULP3 p.Ala386Val (c.1157C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TULP3 p.Ala386Val (c.1157C>T) in the general population?

TULP3 p.Ala386Val (c.1157C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about TULP3 p.Ala386Val (c.1157C>T)?

AlphaMissense predicts likely pathogenic (score 0.9663) — an in-silico prediction, not a clinical call.

TULP3 p.Ala386Val

c.1157C>T · rs371955902 · VCV2464071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9663 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9663	likely pathogenic
REVEL	0.959	strongly pathogenic-leaning
SaProt	LLR -12.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 48 kb · p 0.45 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0022% South Asian · 2/91,074 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.00031% 5/1,614,122 alleles · very rare exomes 5/1,461,850 · genomes 0/152,272 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,537
European (non-Finnish)	0.000254%	393,340

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.Ala386Val
Coding: c.1157C>T
MANE Select: NM_003324
dbSNP: rs371955902
Type: single nucleotide variant
Location: chr12:2938247 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.51 · 1 PDB
Residue 386: 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.Ala386= Likely benign ★ 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
TULP3 c.*1136C>T 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-ala386val (accessed [today's date]).

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