Is TULP1 p.Arg45Ser (c.135G>C) pathogenic?

TULP1 p.Arg45Ser (c.135G>C) is classified Uncertain significance in TULP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-26). AlphaMissense: likely benign (0.2422); Very rare (popmax 0.00329%, nfe).

How common is TULP1 p.Arg45Ser (c.135G>C) in the general population?

TULP1 p.Arg45Ser (c.135G>C) is very rare (popmax 0.00329%, nfe) (gnomAD).

What do computational predictors say about TULP1 p.Arg45Ser (c.135G>C)?

AlphaMissense predicts likely benign (score 0.2422) — an in-silico prediction, not a clinical call.

TULP1 p.Arg45Ser

c.135G>C · rs1237699541 · VCV1018718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2422 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2422	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -6.38	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 1.9	GERP 0.17, phastCons 0.019
Regional constraint	o/e 1.05	unconstrained · MANE · 3,598 bp · p 0.36 · regional, not allelic
Overall
CADD	13.44	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 0.00329% European (non-Finnish) · 35/1,064,918 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00211%

Overall 0.00261% 36/1,378,058 alleles · very rare exomes 36/1,226,054 · genomes 0/152,004 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00329%	30,426
Remaining individualsnot grpmax-eligible	0.00191%	52,352

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: TULP1
Protein: p.Arg45Ser
Coding: c.135G>C
MANE Select: NM_003322
dbSNP: rs1237699541
Type: single nucleotide variant
Location: chr6:35512235 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 45: the 'disordered' region

Full TULP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TULP1 c.1112+1G>A Likely pathogenic ★★ same type
TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same type
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same type
TULP1 c.718+2T>C Pathogenic ★★ same type
TULP1 c.99+1G>A Pathogenic/Likely pathogenic ★★ same type
TULP1 c.999+5G>C Pathogenic/Likely pathogenic ★★ same type
TULP1 p.Arg311Gln Pathogenic/Likely pathogenic ★★ same type
TULP1 p.Arg311Trp Pathogenic/Likely pathogenic ★★ same type

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/tulp1-p-arg45ser (accessed [today's date]).

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