Is TRAP1 p.Ala50Ser (c.148G>T) pathogenic?

TRAP1 p.Ala50Ser (c.148G>T) is classified Uncertain significance in TRAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.0778); Ultra-rare (popmax 0.0212%, amr).

How common is TRAP1 p.Ala50Ser (c.148G>T) in the general population?

TRAP1 p.Ala50Ser (c.148G>T) is ultra-rare (popmax 0.0212%, amr) (gnomAD).

What do computational predictors say about TRAP1 p.Ala50Ser (c.148G>T)?

AlphaMissense predicts likely benign (score 0.0778) — an in-silico prediction, not a clinical call.

TRAP1 p.Ala50Ser

c.148G>T · VCV3328504

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0778 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0212%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0778	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.32	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 -0.18	GERP 0.44
Regional constraint	o/e 1.33	unconstrained · MANE · 59 kb · p 5.2e-24 · regional, not allelic
Overall
CADD	8.036	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0212% Admixed American · 12/56,692 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00957%

Overall 0.00289% 46/1,590,830 alleles · ultra-rare exomes 41/1,438,626 · genomes 5/152,204 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0212%	4,724
Remaining individualsnot grpmax-eligible	0.00489%	20,463
Ashkenazi Jewishnot grpmax-eligible	0.00344%	29,040
European (non-Finnish)	0.0024%	41,749
East Asian	0.00235%	42,472
African / African-American	0.00136%	73,532

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.Ala50Ser
Coding: c.148G>T
MANE Select: NM_016292
Type: single nucleotide variant
Location: chr16:3690926 (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.Ala50Pro Uncertain significance ★ ⚠ same residue
TRAP1 p.Ala50Val Likely benign ★ same residue
TRAP1 p.Ala319Val Uncertain significance ★★ ⚠ same type
TRAP1 p.Ala409Thr 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

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-ala50ser (accessed [today's date]).

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