TRMU p.Ala3=

Q: Is TRMU p.Ala3= (c.9C>G) pathogenic?

TRMU p.Ala3= (c.9C>G) is classified Benign in TRMU (ClinVar, Multiple submitters, 6 submitters; last evaluated 2023-01-29). Common (popmax 9.28%, afr) — too common for a highly-penetrant pathogenic allele; Associated with acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins.

Q: What condition is associated with TRMU p.Ala3= (c.9C>G)?

TRMU p.Ala3= (c.9C>G) is associated with acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (ClinVar).

Q: How common is TRMU p.Ala3= (c.9C>G) in the general population?

TRMU p.Ala3= (c.9C>G) is common (popmax 9.28%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.9C>G · rs75417986 · VCV137719

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 9.28%, afr) — too common for a highly-penetrant pathogenic allele

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.28	GERP -2.6, phastCons 0.057
Overall
CADD	5.175	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.28% African / African-American · 6,807/73,314 alleles

Filtering AF 9.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.02%

Overall 0.525% 8,154/1,552,408 alleles · common exomes 4,010/1,400,122 · genomes 4,144/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.28%	11
Admixed American	0.741%	135
Remaining individualsnot grpmax-eligible	0.697%	143
Ashkenazi Jewishnot grpmax-eligible	0.477%	210
Middle Eastern	0.455%	220
European (non-Finnish)	0.0305%	3,275
South Asian	0.0247%	4,053
Finnishnot grpmax-eligible	0.00195%	51,330

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.Ala3=
Coding: c.9C>G
MANE Select: NM_018006
dbSNP: rs75417986
Type: single nucleotide variant
Location: chr22:46335773 (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-ala3 (accessed [today's date]).

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