Is TRMU p.Cys61Phe (c.182G>T) pathogenic?

TRMU p.Cys61Phe (c.182G>T) is classified Uncertain significance in TRMU (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-01). AlphaMissense: likely pathogenic (0.9698); Very rare (popmax 0.00667%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRMU p.Cys61Phe (c.182G>T)?

TRMU p.Cys61Phe (c.182G>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRMU p.Cys61Phe (c.182G>T) in the general population?

TRMU p.Cys61Phe (c.182G>T) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about TRMU p.Cys61Phe (c.182G>T)?

AlphaMissense predicts likely pathogenic (score 0.9698) — an in-silico prediction, not a clinical call.

TRMU p.Cys61Phe

c.182G>T · rs747301946 · VCV593056

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9698 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9698	likely pathogenic · top 5% in TRMU
REVEL	0.861	moderately pathogenic-leaning
SaProt	LLR -14.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 21 kb · p 0.086 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,932 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000372% 6/1,614,118 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,986
Admixed American	0.00167%	60,010

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.Cys61Phe
Coding: c.182G>T
MANE Select: NM_018006
dbSNP: rs747301946
Type: single nucleotide variant
Location: chr22:46337878 (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.Gly193Trp 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-cys61phe (accessed [today's date]).

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