Is TRRAP p.Pro500= (c.1500A>C) pathogenic?

TRRAP p.Pro500= (c.1500A>C) is classified Likely benign in TRRAP (ClinVar, Single submitter, 2 submitters; last evaluated 2023-05-01). Rare (popmax 0.101%, eas).

How common is TRRAP p.Pro500= (c.1500A>C) in the general population?

TRRAP p.Pro500= (c.1500A>C) is rare (popmax 0.101%, eas) (gnomAD).

TRRAP p.Pro500=

c.1500A>C · rs781811166 · VCV2657700

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.101%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.011	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5	GERP -3.4
Overall
CADD	0.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.101% East Asian · 28/27,692 alleles

Filtering AF 0.0718% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.062%

Overall 0.0417% 555/1,330,918 alleles · rare exomes 525/1,203,978 · genomes 30/126,940 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.123%	816
East Asiangrpmax	0.101%	989
Ashkenazi Jewishnot grpmax-eligible	0.085%	1,176
Finnishnot grpmax-eligible	0.0813%	1,229
Remaining individualsnot grpmax-eligible	0.0739%	1,352
South Asian	0.0565%	1,770
European (non-Finnish)	0.036%	2,775
Admixed American	0.0354%	2,821
African / African-American	0.033%	3,026

Amish 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: TRRAP
Protein: p.Pro500=
Coding: c.1500A>C
MANE Select: NM_001375524
dbSNP: rs781811166
Type: single nucleotide variant
Location: chr7:98910205 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 500: the 'disordered' region

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

Similar variants

TRRAP p.Pro500Arg Uncertain significance ★ ⚠ same residue
TRRAP p.Arg1035Gln Pathogenic/Likely pathogenic ★★ same type
TRRAP p.Glu1104Gly Pathogenic/Likely pathogenic ★★ same type
TRRAP p.Glu1106Lys Likely pathogenic ★★ same type
TRRAP p.Met3318Val Pathogenic/Likely pathogenic ★★ same type
TRRAP p.Val1030Ile Likely pathogenic ★★ same type
TRRAP c.2622+3A>G Uncertain significance ★★ same type
TRRAP c.7176+4A>G 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/trrap-p-pro500 (accessed [today's date]).

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