Is TRIP12 p.Pro282Ser (c.844C>T) pathogenic?

TRIP12 p.Pro282Ser (c.844C>T) is classified Uncertain significance in TRIP12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely pathogenic (0.793); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with TRIP12 p.Pro282Ser (c.844C>T)?

TRIP12 p.Pro282Ser (c.844C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRIP12 p.Pro282Ser (c.844C>T) in the general population?

TRIP12 p.Pro282Ser (c.844C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about TRIP12 p.Pro282Ser (c.844C>T)?

AlphaMissense predicts likely pathogenic (score 0.793) — an in-silico prediction, not a clinical call.

TRIP12 p.Pro282Ser

c.844C>T · VCV3810764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.793 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.793	likely pathogenic
REVEL	0.353	indeterminate
SaProt	LLR -4.98	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 21 kb · p 0.78 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P240S vs ClinVar P282S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,076 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00118% 19/1,614,064 alleles · very rare exomes 18/1,461,882 · genomes 1/152,182 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,359
European (non-Finnish)	0.00136%	73,752

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: TRIP12
Protein: p.Pro282Ser
Coding: c.844C>T
MANE Select: NM_001348323
Type: single nucleotide variant
Location: chr2:229858955 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.06 · 5 PDB
Residue 240 UniProt numbering: the 'disordered' region

Full TRIP12 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

TRIP12 c.4215+4A>G Uncertain significance ★★ same condition
TRIP12 p.Ala1042Val Uncertain significance ★★ ⚠ same condition
TRIP12 p.Ala1766Thr Uncertain significance ★★ ⚠ same condition
TRIP12 p.Arg1666His Uncertain significance ★★ ⚠ same condition
TRIP12 p.Arg1803Trp Uncertain significance ★★ same condition
TRIP12 p.Arg275Leu Uncertain significance ★★ ⚠ same condition
TRIP12 p.Arg33Gly Uncertain significance ★★ ⚠ same condition
TRIP12 p.Asn1536Tyr 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/trip12-p-pro282ser (accessed [today's date]).

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