Is TUFT1 p.Arg285Pro (c.854G>C) pathogenic?

TUFT1 p.Arg285Pro (c.854G>C) is classified Uncertain significance in TUFT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely pathogenic (0.9723); Very rare (popmax 0.00346%, sas); Associated with Inborn genetic diseases.

What condition is associated with TUFT1 p.Arg285Pro (c.854G>C)?

TUFT1 p.Arg285Pro (c.854G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TUFT1 p.Arg285Pro (c.854G>C) in the general population?

TUFT1 p.Arg285Pro (c.854G>C) is very rare (popmax 0.00346%, sas) (gnomAD).

What do computational predictors say about TUFT1 p.Arg285Pro (c.854G>C)?

AlphaMissense predicts likely pathogenic (score 0.9723) — an in-silico prediction, not a clinical call.

TUFT1 p.Arg285Pro

c.854G>C · VCV4194060

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9723 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00346%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9723	likely pathogenic · top 1% in TUFT1
REVEL	0.407	indeterminate
SaProt	LLR -14.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 41 kb · p 0.17 · regional, not allelic
Overall
CADD	32.0	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 0.00346% South Asian · 3/86,780 alleles

Filtering AF 0.000918% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000455%

Overall 0.000442% 7/1,582,460 alleles · very rare exomes 5/1,430,256 · genomes 2/152,204 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00346%	28,927
Remaining individualsnot grpmax-eligible	0.00163%	61,206
European (non-Finnish)	0.000258%	387,689

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: TUFT1
Protein: p.Arg285Pro
Coding: c.854G>C
MANE Select: NM_020127
Type: single nucleotide variant
Location: chr1:151578756 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.66

Full TUFT1 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

TUFT1 p.Ala282Thr Uncertain significance ★ ⚠ same condition
TUFT1 p.Arg117Gln Uncertain significance ★ ⚠ same condition
TUFT1 p.Arg117Trp Uncertain significance ★ ⚠ same condition
TUFT1 p.Arg173Thr Uncertain significance ★ ⚠ same condition
TUFT1 p.Arg27Gly Uncertain significance ★ ⚠ same condition
TUFT1 p.Arg300Gln Uncertain significance ★ ⚠ same condition
TUFT1 p.Arg303Gln Uncertain significance ★ ⚠ same condition
TUFT1 p.Arg362Gln 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/tuft1-p-arg285pro (accessed [today's date]).

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