Is TRRAP p.Pro202Leu (c.605C>T) pathogenic?

TRRAP p.Pro202Leu (c.605C>T) is classified Conflicting classifications of pathogenicity in TRRAP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.1096); Ultra-rare (popmax 0.0223%, eas); Associated with Inborn genetic diseases.

What condition is associated with TRRAP p.Pro202Leu (c.605C>T)?

TRRAP p.Pro202Leu (c.605C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRRAP p.Pro202Leu (c.605C>T) in the general population?

TRRAP p.Pro202Leu (c.605C>T) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about TRRAP p.Pro202Leu (c.605C>T)?

AlphaMissense predicts likely benign (score 0.1096) — an in-silico prediction, not a clinical call.

TRRAP p.Pro202Leu

c.605C>T · rs372524646 · VCV1937265

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1096 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1096	likely benign
REVEL	0.302	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 29 kb · p 1.3e-20 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,876 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00917%

Overall 0.00149% 24/1,613,954 alleles · ultra-rare exomes 20/1,461,890 · genomes 4/152,064 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,488
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0032%	31,254
Admixed American	0.00167%	59,980
Finnishnot grpmax-eligible	0.00156%	63,996
European (non-Finnish)	0.000763%	131,109

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.Pro202Leu
Coding: c.605C>T
MANE Select: NM_001375524
dbSNP: rs372524646
Type: single nucleotide variant
Location: chr7:98897838 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRRAP p.Pro202= Likely benign ★ same residue
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

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-pro202leu (accessed [today's date]).

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