LARS2 p.Val786=

Q: Is LARS2 p.Val786= (c.2358A>G) pathogenic?

LARS2 p.Val786= (c.2358A>G) is classified Benign in LARS2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome.

Q: What condition is associated with LARS2 p.Val786= (c.2358A>G)?

LARS2 p.Val786= (c.2358A>G) is associated with hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome, Perrault syndrome 4 (ClinVar).

Q: How common is LARS2 p.Val786= (c.2358A>G) in the general population?

LARS2 p.Val786= (c.2358A>G) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2358A>G · rs267220 · VCV226704

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.3	GERP -1.8, phastCons 1
Overall
CADD	5.613	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 44,856/44,864 alleles

Filtering AF 99.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.6%

Overall 97.6% 1,574,366/1,613,866 alleles · common exomes 1,440,007/1,461,746 · genomes 134,359/152,120 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	100%	1
Finnishnot grpmax-eligible	100%	1
East Asiangrpmax	100%	1
European (non-Finnish)	99.8%	1
Ashkenazi Jewishnot grpmax-eligible	99.6%	1
Middle Eastern	97.2%	1
Admixed American	96.8%	1
Remaining individualsnot grpmax-eligible	96.7%	1
South Asian	96.5%	1
African / African-American	59.6%	2

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: LARS2
Protein: p.Val786=
Coding: c.2358A>G
MANE Select: NM_015340
dbSNP: rs267220
Type: single nucleotide variant
Location: chr3:45524062 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.57

Full LARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Perrault syndrome 4

For Hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome (Orphanet):

Onset: Neonatal

Similar variants

LARS2 c.235-2A>G Likely pathogenic ★★ same condition
LARS2 p.Arg228His Likely pathogenic ★★ same condition
LARS2 p.Arg663Trp Pathogenic/Likely pathogenic ★★ same condition
LARS2 p.Arg66Ter Pathogenic/Likely pathogenic ★★ same condition
LARS2 p.Asn153His Pathogenic/Likely pathogenic ★★ same condition
LARS2 p.Asp438Gly Likely pathogenic ★★ ⚠ same condition
LARS2 p.Gln147Pro Likely pathogenic ★★ ⚠ same condition
LARS2 p.Glu294Lys 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/lars2-p-val786 (accessed [today's date]).

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