Is TRIP11 p.Phe164= (c.492T>C) pathogenic?

TRIP11 p.Phe164= (c.492T>C) is classified Conflicting classifications of pathogenicity in TRIP11 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-23). Rare (popmax 0.198%, eas); Associated with achondrogenesis type IA.

What condition is associated with TRIP11 p.Phe164= (c.492T>C)?

TRIP11 p.Phe164= (c.492T>C) is associated with achondrogenesis type IA (ClinVar).

How common is TRIP11 p.Phe164= (c.492T>C) in the general population?

TRIP11 p.Phe164= (c.492T>C) is rare (popmax 0.198%, eas) (gnomAD).

How is Achondrogenesis inherited?

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

TRIP11 p.Phe164=

c.492T>C · rs367632896 · VCV390192

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.198%, eas)

Conditions

achondrogenesis type IA

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -4
Overall
CADD	5.977	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.198% East Asian · 89/44,882 alleles

Filtering AF 0.165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.153%

Overall 0.00923% 149/1,614,160 alleles · rare exomes 117/1,461,872 · genomes 32/152,288 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.198%	504
Remaining individualsnot grpmax-eligible	0.04%	2,500
South Asian	0.0253%	3,960
African / African-American	0.00533%	18,760
European (non-Finnish)	0.000678%	147,502

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.Phe164=
Coding: c.492T>C
MANE Select: NM_004239
dbSNP: rs367632896
Type: single nucleotide variant
Location: chr14:92021652 (GRCh38)
Gene constraint: LOEUF 0.731 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.78
Residue 164: a UniProt-annotated variant site (in odcd1; in-frame exon 4 skipping; due to a nucleotide substitution that may also cause protein truncation)

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-phe164 (accessed [today's date]).

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