Is TRRAP p.Ser2058= (c.6174C>T) pathogenic?

TRRAP p.Ser2058= (c.6174C>T) is classified Likely benign in TRRAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-08). Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRRAP p.Ser2058= (c.6174C>T)?

TRRAP p.Ser2058= (c.6174C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRRAP p.Ser2058= (c.6174C>T) in the general population?

TRRAP p.Ser2058= (c.6174C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

TRRAP p.Ser2058=

c.6174C>T · rs781783001 · VCV1896274

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.106	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9	GERP -3.3
Overall
CADD	0.115	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,946 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.0013% 21/1,614,110 alleles · very rare exomes 17/1,461,892 · genomes 4/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,736
Remaining individualsnot grpmax-eligible	0.0048%	20,830
Admixed American	0.00167%	59,998
South Asian	0.0011%	91,090
European (non-Finnish)	0.00102%	98,338

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.Ser2058=
Coding: c.6174C>T
MANE Select: NM_001375524
dbSNP: rs781783001
Type: single nucleotide variant
Location: chr7:98956476 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 2058: an α-helix; the 'interaction with tp53' region

Full TRRAP 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

TRRAP c.8247+5G>T Uncertain significance ★★ same condition
TRRAP p.Ala1055Thr Uncertain significance ★★ same condition
TRRAP p.Ala1880Val Uncertain significance ★★ ⚠ same condition
TRRAP p.Ala1895Val Uncertain significance ★★ same condition
TRRAP p.Ala1995Thr Uncertain significance ★★ same condition
TRRAP p.Ala2656Thr Uncertain significance ★★ ⚠ same condition
TRRAP p.Ala322Ser Uncertain significance ★★ ⚠ same condition
TRRAP p.Ala3616Thr 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/trrap-p-ser2058 (accessed [today's date]).

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