Is PTCD3 p.Phe583fs (c.1746_1747dup) pathogenic?

PTCD3 p.Phe583fs (c.17461747dup) is classified Pathogenic in PTCD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-02-08). Ultra-rare (popmax 0.0245%, eas); Associated with combined oxidative phosphorylation deficiency 51.

What condition is associated with PTCD3 p.Phe583fs (c.1746_1747dup)?

PTCD3 p.Phe583fs (c.1746_1747dup) is associated with combined oxidative phosphorylation deficiency 51 (ClinVar).

How common is PTCD3 p.Phe583fs (c.1746_1747dup) in the general population?

PTCD3 p.Phe583fs (c.1746_1747dup) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

PTCD3 p.Phe583fs

c.1746_1747dup · rs1573859565 · VCV982043

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Conditions

combined oxidative phosphorylation deficiency 51

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 21 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.41	GERP 1.2, phastCons 0.97

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,880 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.000681% 11/1,614,134 alleles · ultra-rare exomes 11/1,461,850 · genomes 0/152,284 · joint denominator

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: PTCD3
Protein: p.Phe583fs
Coding: c.1746_1747dup
MANE Select: NM_017952
dbSNP: rs1573859565
Type: Microsatellite
Location: chr2:86134952 (GRCh38)
Gene constraint: LOEUF 1.132 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 86 PDB
Residue 583: an α-helix

Full PTCD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined oxidative phosphorylation deficiency 51 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTCD3 p.Leu95fs Likely pathogenic ★ same condition
PTCD3 p.Arg524Leu Uncertain significance ★★ ⚠ same condition
PTCD3 c.1630-1G>A Likely pathogenic ★ same condition
PTCD3 c.1979+1G>A Likely pathogenic ★ same condition
PTCD3 c.805-2A>G Likely pathogenic ★ same condition
PTCD3 p.Thr237fs Likely pathogenic ★ same condition
PTCD3 p.Trp477Ter Likely pathogenic ★ same condition
PTCD3 p.Asp676fs Uncertain significance ★ 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/ptcd3-p-phe583fs (accessed [today's date]).

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