Is TRIP11 p.Lys366= (c.1098G>A) pathogenic?

TRIP11 p.Lys366= (c.1098G>A) is classified Benign in TRIP11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). Rare (popmax 0.379%, eas); Associated with achondrogenesis type IA.

What condition is associated with TRIP11 p.Lys366= (c.1098G>A)?

TRIP11 p.Lys366= (c.1098G>A) is associated with achondrogenesis type IA (ClinVar).

How common is TRIP11 p.Lys366= (c.1098G>A) in the general population?

TRIP11 p.Lys366= (c.1098G>A) is rare (popmax 0.379%, eas) (gnomAD).

How is Achondrogenesis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TRIP11 p.Lys366=

c.1098G>A · rs201503194 · VCV1599678

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.379%, eas)

Conditions

achondrogenesis type IA

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.028	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.13	GERP -2.3, phastCons 0.004
Overall
CADD	2.506	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.379% East Asian · 170/44,854 alleles

Filtering AF 0.332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.315%

Overall 0.0113% 182/1,614,098 alleles · rare exomes 173/1,461,742 · genomes 9/152,356 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.379%	264
Remaining individualsnot grpmax-eligible	0.0176%	5,682
European (non-Finnish)	8.47e-05%	1,179,999

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: TRIP11
Protein: p.Lys366=
Coding: c.1098G>A
MANE Select: NM_004239
dbSNP: rs201503194
Type: single nucleotide variant
Location: chr14:92014303 (GRCh38)
Gene constraint: LOEUF 0.731 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.78
Residue 366: a UniProt-annotated variant site (in odcd1; due to a nucleotide substitution that causes protein truncation or in-frame exon 4 skipping); a UniProt-annotated variant site (in acg1a and odcd1)

Full TRIP11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

achondrogenesis type IA — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Achondrogenesis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (France)

Similar variants

TRIP11 p.Arg1028Ter Pathogenic/Likely pathogenic ★★ same condition
TRIP11 p.Arg255Ter Pathogenic ★★ same condition
TRIP11 p.Arg264Ter Pathogenic ★★ same condition
TRIP11 p.Arg871Ter Pathogenic ★★ same condition
TRIP11 p.Gln1758Ter Pathogenic/Likely pathogenic ★★ same condition
TRIP11 p.Leu1321Ter Pathogenic/Likely pathogenic ★★ same condition
TRIP11 p.Trp1224Ter Pathogenic ★★ same condition
TRIP11 c.5719+2T>C 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/trip11-p-lys366 (accessed [today's date]).

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