Is TRMU p.Asp288= (c.864C>T) pathogenic?

TRMU p.Asp288= (c.864C>T) is classified Benign in TRMU (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Low-frequency (popmax 4.15%, afr); Associated with acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins.

How common is TRMU p.Asp288= (c.864C>T) in the general population?

TRMU p.Asp288= (c.864C>T) is low-frequency (popmax 4.15%, afr) (gnomAD).

TRMU p.Asp288=

Q: What condition is associated with TRMU p.Asp288= (c.864C>T)?

TRMU p.Asp288= (c.864C>T) is associated with acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (ClinVar).

Q: How is Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.864C>T · rs61737827 · VCV137713

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.15%, afr)

Conditions

acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8	GERP -1.2
Overall
CADD	3.561	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.15% African / African-American · 3,110/74,944 alleles

Filtering AF 4.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.98%

Overall 0.255% 4,116/1,613,438 alleles · low-frequency exomes 2,250/1,461,288 · genomes 1,866/152,150 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.15%	24
Middle Eastern	1.12%	89
Admixed American	0.397%	252
Remaining individualsnot grpmax-eligible	0.391%	256
South Asian	0.0593%	1,686
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,741
European (non-Finnish)	0.032%	3,129
East Asian	0.0156%	6,405
Finnishnot grpmax-eligible	0.00156%	63,926

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.Asp288=
Coding: c.864C>T
MANE Select: NM_018006
dbSNP: rs61737827
Type: single nucleotide variant
Location: chr22:46353858 (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

acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

TRMU c.1019-1G>A Likely pathogenic ★★ same condition
TRMU c.1102-3C>G Likely pathogenic ★★ same condition
TRMU c.249-2A>G Likely pathogenic ★★ same condition
TRMU c.355+1G>C Likely pathogenic ★★ same condition
TRMU c.355+1G>T Likely pathogenic ★★ same condition
TRMU c.652-2A>G Likely pathogenic ★★ same condition
TRMU c.706-1G>A Pathogenic ★★ same condition
TRMU c.706-2A>G Pathogenic/Likely pathogenic ★★ 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-asp288 (accessed [today's date]).

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