Is TRAP1 p.Ala41Val (c.122C>T) pathogenic?

TRAP1 p.Ala41Val (c.122C>T) is classified Likely benign in TRAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.0704); Very rare (popmax 0.000603%, nfe).

How common is TRAP1 p.Ala41Val (c.122C>T) in the general population?

TRAP1 p.Ala41Val (c.122C>T) is very rare (popmax 0.000603%, nfe) (gnomAD).

What do computational predictors say about TRAP1 p.Ala41Val (c.122C>T)?

AlphaMissense predicts likely benign (score 0.0704) — an in-silico prediction, not a clinical call.

TRAP1 p.Ala41Val

c.122C>T · VCV4190033

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0704 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000603%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0704	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.88	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 1.4	GERP -3.2, phastCons 0.17
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	3.765	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 0.000603% European (non-Finnish) · 7/1,161,052 alleles

Filtering AF 0.000251% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000161%

Overall 0.000494% 7/1,418,098 alleles · very rare

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: TRAP1
Protein: p.Ala41Val
Coding: c.122C>T
MANE Select: NM_016292
Type: single nucleotide variant
Location: chr16:3690952 (GRCh38)
Gene constraint: LOEUF 1.343 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 24 PDB

Full TRAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAP1 p.Ala319Val Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala409Thr Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala50Ser Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala64Thr Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala659Thr Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala7Val Uncertain significance ★★ ⚠ same type
TRAP1 p.Arg271Pro Uncertain significance ★★ ⚠ same type
TRAP1 p.Arg340His 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/trap1-p-ala41val (accessed [today's date]).

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