Is TRMU p.Arg5Pro (c.14G>C) pathogenic?

TRMU p.Arg5Pro (c.14G>C) is classified Uncertain significance in TRMU (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-09). AlphaMissense: ambiguous (0.428); Ultra-rare (popmax 0.0133%, amr); Associated with Inborn genetic diseases.

What condition is associated with TRMU p.Arg5Pro (c.14G>C)?

TRMU p.Arg5Pro (c.14G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRMU p.Arg5Pro (c.14G>C) in the general population?

TRMU p.Arg5Pro (c.14G>C) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about TRMU p.Arg5Pro (c.14G>C)?

AlphaMissense predicts ambiguous (score 0.428) — an in-silico prediction, not a clinical call.

TRMU p.Arg5Pro

c.14G>C · rs568649964 · VCV2248857

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.428 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.428	ambiguous
REVEL	0.768	pathogenic-leaning
SaProt	LLR -6.16	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 21 kb · p 0.086 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 7/52,572 alleles

Filtering AF 0.00622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00434%

Overall 0.000579% 9/1,554,142 alleles · ultra-rare exomes 5/1,401,818 · genomes 4/152,324 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,510
South Asian	0.00117%	85,302
European (non-Finnish)	8.67e-05%	1,154,017

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: TRMU
Protein: p.Arg5Pro
Coding: c.14G>C
MANE Select: NM_018006
dbSNP: rs568649964
Type: single nucleotide variant
Location: chr22:46335778 (GRCh38)
Gene constraint: LOEUF 1.276 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.60

Full TRMU 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

TRMU p.Ala268Thr Uncertain significance ★★ ⚠ same condition
TRMU p.Arg26Gln Uncertain significance ★★ ⚠ same condition
TRMU p.Arg306Ser Uncertain significance ★★ ⚠ same condition
TRMU p.Arg309Cys Uncertain significance ★★ ⚠ same condition
TRMU p.Arg385Trp Uncertain significance ★★ ⚠ same condition
TRMU p.Cys222Tyr Uncertain significance ★★ ⚠ same condition
TRMU p.Cys377Trp Uncertain significance ★★ ⚠ same condition
TRMU p.Cys61Phe 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/trmu-p-arg5pro (accessed [today's date]).

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