Is TRRAP p.Ala2= (c.6G>A) pathogenic?

TRRAP p.Ala2= (c.6G>A) is classified Likely benign in TRRAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-01). Ultra-rare (popmax 0.0599%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRRAP p.Ala2= (c.6G>A)?

TRRAP p.Ala2= (c.6G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TRRAP p.Ala2= (c.6G>A) in the general population?

TRRAP p.Ala2= (c.6G>A) is ultra-rare (popmax 0.0599%, nfe) (gnomAD).

TRRAP p.Ala2=

c.6G>A · rs146782965 · VCV2052555

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0599%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.2	GERP -3.4
Overall
CADD	2.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0599% European (non-Finnish) · 704/1,174,636 alleles

Filtering AF 0.0563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0547%

Overall 0.0473% 758/1,602,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0599%	1,669
Remaining individualsnot grpmax-eligible	0.0258%	3,876
African / African-American	0.0242%	4,129
South Asian	0.0134%	7,443
Finnishnot grpmax-eligible	0.00783%	12,774
Admixed American	0.00344%	29,036
Ashkenazi Jewishnot grpmax-eligible	0.00341%	29,350

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.Ala2=
Coding: c.6G>A
MANE Select: NM_001375524
dbSNP: rs146782965
Type: single nucleotide variant
Location: chr7:98881156 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 2: a modified residue (n-acetylalanine)

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-ala2 (accessed [today's date]).

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