Is FASTKD2 p.Ser708= (c.2124C>T) pathogenic?

FASTKD2 p.Ser708= (c.2124C>T) is classified Likely benign in FASTKD2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-16). Rare (popmax 0.18%, sas); Associated with combined oxidative phosphorylation deficiency 44.

What condition is associated with FASTKD2 p.Ser708= (c.2124C>T)?

FASTKD2 p.Ser708= (c.2124C>T) is associated with combined oxidative phosphorylation deficiency 44 (ClinVar).

How common is FASTKD2 p.Ser708= (c.2124C>T) in the general population?

FASTKD2 p.Ser708= (c.2124C>T) is rare (popmax 0.18%, sas) (gnomAD).

FASTKD2 p.Ser708=

c.2124C>T · rs200616436 · VCV1219083

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.18%, sas)

Conditions

combined oxidative phosphorylation deficiency 44

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 0.012	GERP -2.2
Overall
CADD	2.545	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.18% South Asian · 164/91,062 alleles

Filtering AF 0.158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.149%

Overall 0.0161% 260/1,612,566 alleles · rare exomes 239/1,460,380 · genomes 21/152,186 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.18%	555
Middle Eastern	0.134%	749
Ashkenazi Jewishnot grpmax-eligible	0.0406%	2,466
Remaining individualsnot grpmax-eligible	0.0224%	4,459
Admixed American	0.0217%	4,614
European (non-Finnish)	0.00407%	24,573
African / African-American	0.00134%	74,896

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: FASTKD2
Protein: p.Ser708=
Coding: c.2124C>T
MANE Select: NM_001136193
dbSNP: rs200616436
Type: single nucleotide variant
Location: chr2:206791793 (GRCh38)
Gene constraint: LOEUF 1.203 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.39
Residue 708: a UniProt-annotated variant site (in coxpd44; decreased mitochondrial large ribosomal subunit assembly); a UniProt-annotated variant site (in coxpd44); a modified residue (phosphoserine)

Full FASTKD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined oxidative phosphorylation deficiency 44 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FASTKD2 c.882-1G>A Pathogenic/Likely pathogenic ★★ same condition
FASTKD2 c.991-2A>G Likely pathogenic ★★ same condition
FASTKD2 p.Arg290Ter Pathogenic ★★ same condition
FASTKD2 p.Arg358Ter Pathogenic/Likely pathogenic ★★ same condition
FASTKD2 p.Arg432Ter Pathogenic/Likely pathogenic ★★ same condition
FASTKD2 p.Cys283Ter Pathogenic/Likely pathogenic ★★ same condition
FASTKD2 p.Gln564Ter Pathogenic/Likely pathogenic ★★ same condition
FASTKD2 p.Trp302Ter 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/fastkd2-p-ser708 (accessed [today's date]).

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