Is FARS2 p.Lys202= (c.606G>A) pathogenic?

FARS2 p.Lys202= (c.606G>A) is classified Benign/Likely benign in FARS2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-06-01). Rare (popmax 0.217%, nfe); Associated with combined oxidative phosphorylation defect type 14.

What condition is associated with FARS2 p.Lys202= (c.606G>A)?

FARS2 p.Lys202= (c.606G>A) is associated with combined oxidative phosphorylation defect type 14 (ClinVar).

How common is FARS2 p.Lys202= (c.606G>A) in the general population?

FARS2 p.Lys202= (c.606G>A) is rare (popmax 0.217%, nfe) (gnomAD).

FARS2 p.Lys202=

Q: How is Combined oxidative phosphorylation defect type 14 inherited?

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

c.606G>A · rs17851782 · VCV137290

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.217%, nfe)

Conditions

combined oxidative phosphorylation defect type 14

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 1.3	GERP -3.3, phastCons 0.98
Overall
CADD	7.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.217% European (non-Finnish) · 2,562/1,179,692 alleles

Filtering AF 0.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.207%

Overall 0.175% 2,804/1,605,564 alleles · rare exomes 2,616/1,453,318 · genomes 188/152,246 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.325%	308
European (non-Finnish)grpmax	0.217%	460
Remaining individualsnot grpmax-eligible	0.139%	718
Admixed American	0.04%	2,500
African / African-American	0.0347%	2,885
Finnishnot grpmax-eligible	0.0107%	9,336
South Asian	0.0033%	30,345

Ashkenazi Jewish 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: FARS2
Protein: p.Lys202=
Coding: c.606G>A
MANE Select: NM_006567
dbSNP: rs17851782
Type: single nucleotide variant
Location: chr6:5369176 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.17 · 9 PDB
Residue 202: an α-helix; a modified residue (n6-acetyllysine)

Full FARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined oxidative phosphorylation defect type 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined oxidative phosphorylation defect type 14 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

FARS2 p.Arg307Ter Pathogenic/Likely pathogenic ★★ same condition
FARS2 p.Arg386Ter Pathogenic/Likely pathogenic ★★ same condition
FARS2 p.Arg419Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
FARS2 p.Arg419His Pathogenic/Likely pathogenic ★★ same condition
FARS2 p.Gln100Ter Pathogenic/Likely pathogenic ★★ same condition
FARS2 p.Gln216Ter Pathogenic ★★ same condition
FARS2 p.Gly309Ser Pathogenic/Likely pathogenic ★★ same condition
FARS2 p.Pro361Leu 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/fars2-p-lys202 (accessed [today's date]).

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