Is TRIP11 p.Ser3= (c.9C>T) pathogenic?

TRIP11 p.Ser3= (c.9C>T) is classified Conflicting classifications of pathogenicity in TRIP11 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-26). Rare (popmax 0.164%, afr); Associated with achondrogenesis type IA.

What condition is associated with TRIP11 p.Ser3= (c.9C>T)?

TRIP11 p.Ser3= (c.9C>T) is associated with achondrogenesis type IA (ClinVar).

How common is TRIP11 p.Ser3= (c.9C>T) in the general population?

TRIP11 p.Ser3= (c.9C>T) is rare (popmax 0.164%, afr) (gnomAD).

How is Achondrogenesis inherited?

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

TRIP11 p.Ser3=

c.9C>T · rs148398142 · VCV885548

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.164%, afr)

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 0.92	GERP 0.037, phastCons 1
Overall
CADD	13.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.164% African / African-American · 123/75,048 alleles

Filtering AF 0.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.131%

Overall 0.00788% 127/1,612,202 alleles · rare exomes 48/1,459,844 · genomes 79/152,358 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.164%	610
Remaining individualsnot grpmax-eligible	0.00481%	20,808
Admixed American	0.00167%	59,730

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.Ser3=
Coding: c.9C>T
MANE Select: NM_004239
dbSNP: rs148398142
Type: single nucleotide variant
Location: chr14:92039677 (GRCh38)
Gene constraint: LOEUF 0.731 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.78
Residue 3: the 'amphipathic lipid-packing sensor required for tethering of intra-golgi vesicles' region

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-ser3 (accessed [today's date]).

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