Is TULP1 p.Pro62Arg (c.185C>G) pathogenic?

TULP1 p.Pro62Arg (c.185C>G) is classified Uncertain significance in TULP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-29). AlphaMissense: likely benign (0.0686); No allele count reported in gnomAD v4.1 (AN 1,348,532); Associated with TULP1-related disorder.

What condition is associated with TULP1 p.Pro62Arg (c.185C>G)?

TULP1 p.Pro62Arg (c.185C>G) is associated with TULP1-related disorder (ClinVar).

How common is TULP1 p.Pro62Arg (c.185C>G) in the general population?

TULP1 p.Pro62Arg (c.185C>G) is no allele count reported in gnomAD v4.1 (AN 1,348,532) (gnomAD).

What do computational predictors say about TULP1 p.Pro62Arg (c.185C>G)?

AlphaMissense predicts likely benign (score 0.0686) — an in-silico prediction, not a clinical call.

TULP1 p.Pro62Arg

c.185C>G · VCV3346656

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0686 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,348,532)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TULP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0686	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -6.66	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 2.9	GERP 0.15, phastCons 0.2
Regional constraint	o/e 1.05	unconstrained · MANE · 3,598 bp · p 0.36 · regional, not allelic
Overall
CADD	15.58	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

No allele count reported in gnomAD v4.1 (AN 1,348,532). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TULP1
Protein: p.Pro62Arg
Coding: c.185C>G
MANE Select: NM_003322
Type: single nucleotide variant
Location: chr6:35512185 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 62: the 'disordered' region

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

Disease context

TULP1-related disorder

Similar variants

TULP1 p.Pro62Ser Uncertain significance ★★ ⚠ same residue
TULP1 p.Pro62= Likely benign ★ same residue
TULP1 c.1112+1G>A Likely pathogenic ★★ same condition
TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.718+2T>C Pathogenic ★★ same condition
TULP1 c.999+5G>C Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg342Ter Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg34Ter Pathogenic ★★ 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/tulp1-p-pro62arg (accessed [today's date]).

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