Is TRIP4 p.Pro364= (c.1092A>G) pathogenic?

TRIP4 p.Pro364= (c.1092A>G) is classified Benign in TRIP4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 10.4%, mid) — too common for a highly-penetrant pathogenic allele.

TRIP4 p.Pro364=

Q: How common is TRIP4 p.Pro364= (c.1092A>G) in the general population?

TRIP4 p.Pro364= (c.1092A>G) is common (popmax 10.4%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1092A>G · rs34758599 · VCV1267097

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 10.4%, mid) — too common for a highly-penetrant pathogenic allele

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 0.79	GERP 1.6, phastCons 0.005
Overall
CADD	12.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.4% Middle Eastern · 630/6,062 alleles

Filtering AF 9.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.45%

Overall 6.14% 99,166/1,614,030 alleles · common exomes 91,792/1,461,754 · genomes 7,374/152,276 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	10.6%	9
Middle Easterngrpmax	10.4%	10
South Asian	9.08%	11
Finnishnot grpmax-eligible	7.73%	13
European (non-Finnish)	6.44%	16
Remaining individualsnot grpmax-eligible	6.04%	17
Amishnot grpmax-eligible	5.37%	19
Admixed American	2.65%	38
African / African-American	0.993%	101
East Asian	0.0267%	3,740

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: TRIP4
Protein: p.Pro364=
Coding: c.1092A>G
MANE Select: NM_016213
dbSNP: rs34758599
Type: single nucleotide variant
Location: chr15:64414133 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.54 · 10 PDB
Residue 364: the 'mediates interaction with ufl1' region

Full TRIP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRIP4 c.272-1G>T Likely pathogenic ★★ same type
TRIP4 p.Arg309Ter Pathogenic/Likely pathogenic ★★ same type
TRIP4 p.Arg466Ter Pathogenic/Likely pathogenic ★★ same type
TRIP4 p.Leu20Ter Pathogenic ★★ same type
TRIP4 p.Trp297Ter Pathogenic ★★ same type
TRIP4 p.Ala398Thr Uncertain significance ★★ ⚠ same type
TRIP4 p.Arg104Gln Uncertain significance ★★ ⚠ same type
TRIP4 p.Arg189Cys Uncertain significance ★★ ⚠ same type

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/trip4-p-pro364 (accessed [today's date]).

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