Is FARS2 p.Thr232= (c.696C>T) pathogenic?

FARS2 p.Thr232= (c.696C>T) is classified Likely benign in FARS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-12). Very rare (popmax 0.00195%, nfe); Associated with combined oxidative phosphorylation defect type 14.

What condition is associated with FARS2 p.Thr232= (c.696C>T)?

FARS2 p.Thr232= (c.696C>T) is associated with combined oxidative phosphorylation defect type 14 (ClinVar).

How common is FARS2 p.Thr232= (c.696C>T) in the general population?

FARS2 p.Thr232= (c.696C>T) is very rare (popmax 0.00195%, nfe) (gnomAD).

FARS2 p.Thr232=

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.696C>T · rs190712413 · VCV1155018

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00195%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.42	GERP -1.4, phastCons 0.041
Overall
CADD	7.761	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% European (non-Finnish) · 23/1,179,550 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00508% 82/1,613,394 alleles · very rare exomes 74/1,461,050 · genomes 8/152,344 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0875%	1,143
Remaining individualsnot grpmax-eligible	0.0048%	20,819
European (non-Finnish)grpmax	0.00195%	51,285

Finnish 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.Thr232=
Coding: c.696C>T
MANE Select: NM_006567
dbSNP: rs190712413
Type: single nucleotide variant
Location: chr6:5404625 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.17 · 9 PDB

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.Thr232Ala Uncertain significance ★ ⚠ same residue
FARS2 p.Thr232fs Pathogenic ★ same residue
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

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-thr232 (accessed [today's date]).

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