Is FASTKD2 p.Pro211Arg (c.632C>G) pathogenic?

FASTKD2 p.Pro211Arg (c.632C>G) is classified Likely pathogenic in FASTKD2 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.2457); Very rare (popmax 6.84e-05%); Associated with combined oxidative phosphorylation deficiency 44.

What condition is associated with FASTKD2 p.Pro211Arg (c.632C>G)?

FASTKD2 p.Pro211Arg (c.632C>G) is associated with combined oxidative phosphorylation deficiency 44 (ClinVar).

How common is FASTKD2 p.Pro211Arg (c.632C>G) in the general population?

FASTKD2 p.Pro211Arg (c.632C>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about FASTKD2 p.Pro211Arg (c.632C>G)?

AlphaMissense predicts likely benign (score 0.2457) — an in-silico prediction, not a clinical call.

FASTKD2 p.Pro211Arg

c.632C>G · VCV4278940

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2457 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

combined oxidative phosphorylation deficiency 44

Computational evidence

Protein change
AlphaMissense	0.2457	likely benign ⚠ discordant with ClinVar
REVEL	0.355	indeterminate
SaProt	LLR -9.54	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,840 alleles · very rare

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.Pro211Arg
Coding: c.632C>G
MANE Select: NM_001136193
Type: single nucleotide variant
Location: chr2:206767325 (GRCh38)
Gene constraint: LOEUF 1.203 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.39
Residue 211: a UniProt-annotated variant site (in coxpd44)

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-pro211arg (accessed [today's date]).

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