Is TRIP4 p.Val7Ala (c.20T>C) pathogenic?

TRIP4 p.Val7Ala (c.20T>C) is classified Conflicting classifications of pathogenicity in TRIP4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-10-06). AlphaMissense: likely benign (0.0474); Ultra-rare (popmax 0.0693%, mid); Associated with Inborn genetic diseases.

What condition is associated with TRIP4 p.Val7Ala (c.20T>C)?

TRIP4 p.Val7Ala (c.20T>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRIP4 p.Val7Ala (c.20T>C) in the general population?

TRIP4 p.Val7Ala (c.20T>C) is ultra-rare (popmax 0.0693%, mid) (gnomAD).

What do computational predictors say about TRIP4 p.Val7Ala (c.20T>C)?

AlphaMissense predicts likely benign (score 0.0474) — an in-silico prediction, not a clinical call.

TRIP4 p.Val7Ala

c.20T>C · rs1040878226 · VCV1357132

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0474 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0693%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0474	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -5.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -2.6
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.41 · regional, not allelic
Overall
CADD	4.029	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0693% Middle Eastern · 4/5,776 alleles

Filtering AF 0.0236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0142%

Overall 0.00245% 38/1,547,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0693%	1,444
Remaining individualsnot grpmax-eligible	0.00833%	12,007
European (non-Finnish)	0.00244%	40,959
Admixed American	0.00197%	50,840

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.Val7Ala
Coding: c.20T>C
MANE Select: NM_016213
dbSNP: rs1040878226
Type: single nucleotide variant
Location: chr15:64387883 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.54 · 10 PDB

Full TRIP4 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

TRIP4 p.Val7= Benign ★★ same residue
TRIP4 p.Ala398Thr Uncertain significance ★★ ⚠ same condition
TRIP4 p.Arg104Gln Uncertain significance ★★ ⚠ same condition
TRIP4 p.Arg189Cys Uncertain significance ★★ ⚠ same condition
TRIP4 p.Arg321Gln Uncertain significance ★★ ⚠ same condition
TRIP4 p.Arg492Cys Uncertain significance ★★ ⚠ same condition
TRIP4 p.Asp100Asn Uncertain significance ★★ ⚠ same condition
TRIP4 p.Asp501Glu 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/trip4-p-val7ala (accessed [today's date]).

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