Is LARS1 p.Arg413Ter (c.1237C>T) pathogenic?

LARS1 p.Arg413Ter (c.1237C>T) is classified Pathogenic in LARS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-04). Very rare (popmax 0.00144%, nfe); Associated with acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins.

What condition is associated with LARS1 p.Arg413Ter (c.1237C>T)?

LARS1 p.Arg413Ter (c.1237C>T) is associated with acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (ClinVar).

How common is LARS1 p.Arg413Ter (c.1237C>T) in the general population?

LARS1 p.Arg413Ter (c.1237C>T) is very rare (popmax 0.00144%, nfe) (gnomAD).

LARS1 p.Arg413Ter

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.1237C>T · rs773819736 · VCV2533694

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

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/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 32
Splicing
SpliceAI	Δ0.25	acceptor loss · deltas
Pangolin	Δ0.46	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.2	GERP 0.13, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,178,746 alleles

Filtering AF 0.000879% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00112% 18/1,611,988 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00144%	69,338
African / African-American	0.00134%	74,874

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: LARS1
Protein: p.Arg413Ter
Coding: c.1237C>T
MANE Select: NM_020117
dbSNP: rs773819736
Type: single nucleotide variant
Location: chr5:146153221 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.78 · 8 PDB
Residue 413: the 'editing domain' region; an α-helix

Full LARS1 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

LARS1 p.Arg1105Ter Pathogenic/Likely pathogenic ★★ same condition
LARS1 p.Cys248Phe Likely pathogenic ★ same condition
LARS1 p.Gln221Ter Likely pathogenic ★ same condition
LARS1 p.Ile451Phe Likely pathogenic ★ same condition
LARS1 p.Trp585Ter Likely pathogenic ★ same condition
LARS1 c.2770-2A>G Conflicting classifications of pathogenicity ★ same condition
LARS1 p.Val431Asp Conflicting classifications of pathogenicity ★ ⚠ same condition
LARS1 p.Phe603_Tyr604insTer 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/lars1-p-arg413ter (accessed [today's date]).

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