Is TRRAP p.Ile3626Val (c.10876A>G) pathogenic?

TRRAP p.Ile3626Val (c.10876A>G) is classified Uncertain significance in TRRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely benign (0.0672); No allele count reported in gnomAD v4.1 (AN 1,614,188); Associated with TRRAP-related disorder.

What condition is associated with TRRAP p.Ile3626Val (c.10876A>G)?

TRRAP p.Ile3626Val (c.10876A>G) is associated with TRRAP-related disorder (ClinVar).

How common is TRRAP p.Ile3626Val (c.10876A>G) in the general population?

TRRAP p.Ile3626Val (c.10876A>G) is no allele count reported in gnomAD v4.1 (AN 1,614,188) (gnomAD).

What do computational predictors say about TRRAP p.Ile3626Val (c.10876A>G)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

TRRAP p.Ile3626Val

c.10876A>G · rs2485072148 · VCV2635441

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,188)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

TRRAP-related disorder

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.224	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 3,855 bp · p 4.2e-18 · regional, not allelic
Overall
CADD	22.6	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 is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I3612V vs ClinVar I3626V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,188). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TRRAP
Protein: p.Ile3626Val
Coding: c.10876A>G
MANE Select: NM_001375524
dbSNP: rs2485072148
Type: single nucleotide variant
Location: chr7:99008499 (GRCh38)
Gene constraint: LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)

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

Disease context

TRRAP-related disorder

Similar variants

TRRAP p.Ile3626Met Uncertain significance ★ same residue
TRRAP p.Arg1562Gln Uncertain significance ★★ same condition
TRRAP p.Arg447Gln Uncertain significance ★★ same condition
TRRAP p.Ile3068Val Uncertain significance ★★ ⚠ same condition
TRRAP p.Met3545Ile Uncertain significance ★★ same condition
TRRAP p.Pro3761Leu Uncertain significance ★★ same condition
TRRAP p.Thr2139Ser Uncertain significance ★★ same condition
TRRAP p.Tyr2171Cys 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-ile3626val (accessed [today's date]).

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