Is TULP3 p.Met404Val (c.1210A>G) pathogenic?

TULP3 p.Met404Val (c.1210A>G) is classified Uncertain significance in TULP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-18). AlphaMissense: likely pathogenic (0.6614); Very rare (popmax 0.00627%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TULP3 p.Met404Val (c.1210A>G)?

TULP3 p.Met404Val (c.1210A>G) is associated with Inborn genetic diseases (ClinVar).

How common is TULP3 p.Met404Val (c.1210A>G) in the general population?

TULP3 p.Met404Val (c.1210A>G) is very rare (popmax 0.00627%, nfe) (gnomAD).

What do computational predictors say about TULP3 p.Met404Val (c.1210A>G)?

AlphaMissense predicts likely pathogenic (score 0.6614) — an in-silico prediction, not a clinical call.

TULP3 p.Met404Val

c.1210A>G · rs151194786 · VCV2294330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6614 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00627%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6614	likely pathogenic
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -12.10	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 48 kb · p 0.45 · regional, not allelic
Overall
CADD	25.8	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 0.00627% European (non-Finnish) · 74/1,180,058 alleles

Filtering AF 0.00511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00496% 80/1,614,118 alleles · very rare exomes 75/1,461,888 · genomes 5/152,230 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00627%	15,947
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00267%	37,467
Admixed American	0.00167%	60,006

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.Met404Val
Coding: c.1210A>G
MANE Select: NM_003324
dbSNP: rs151194786
Type: single nucleotide variant
Location: chr12:2939325 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.51 · 1 PDB
Residue 404: 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.Met404Ile Uncertain significance ★ ⚠ 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-met404val (accessed [today's date]).

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