Is TULP1 p.Arg82Gln (c.245G>A) pathogenic?

TULP1 p.Arg82Gln (c.245G>A) is classified Uncertain significance in TULP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). AlphaMissense: likely benign (0.0762); Very rare (popmax 0.00943%, afr).

How common is TULP1 p.Arg82Gln (c.245G>A) in the general population?

TULP1 p.Arg82Gln (c.245G>A) is very rare (popmax 0.00943%, afr) (gnomAD).

What do computational predictors say about TULP1 p.Arg82Gln (c.245G>A)?

AlphaMissense predicts likely benign (score 0.0762) — an in-silico prediction, not a clinical call.

TULP1 p.Arg82Gln

c.245G>A · rs753258431 · VCV967543

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0762 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00943%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0762	likely benign
REVEL	0.129	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 -1.5	GERP -1.5
Regional constraint	o/e 1.05	unconstrained · MANE · 3,598 bp · p 0.36 · regional, not allelic
Overall
CADD	6.058	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 0.00943% African / African-American · 7/74,216 alleles

Filtering AF 0.00441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00311%

Overall 0.00202% 32/1,583,486 alleles · very rare exomes 27/1,431,450 · genomes 5/152,036 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00943%	10,602
European (non-Finnish)	0.00206%	48,561
Admixed American	0.00178%	56,142

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.Arg82Gln
Coding: c.245G>A
MANE Select: NM_003322
dbSNP: rs753258431
Type: single nucleotide variant
Location: chr6:35511752 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 82: the 'disordered' region

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

Similar variants

TULP1 p.Arg82fs Pathogenic ★ same residue
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

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-arg82gln (accessed [today's date]).

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