Is PTCD3 p.Ser389Ter (c.1166C>G) pathogenic?

PTCD3 p.Ser389Ter (c.1166C>G) is classified Likely pathogenic in PTCD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-01). Very rare (popmax 0.00534%, afr); Associated with PTCD3-related disorder.

What condition is associated with PTCD3 p.Ser389Ter (c.1166C>G)?

PTCD3 p.Ser389Ter (c.1166C>G) is associated with PTCD3-related disorder (ClinVar).

How common is PTCD3 p.Ser389Ter (c.1166C>G) in the general population?

PTCD3 p.Ser389Ter (c.1166C>G) is very rare (popmax 0.00534%, afr) (gnomAD).

PTCD3 p.Ser389Ter

c.1166C>G · VCV3348111

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

PTCD3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 24
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.27 · evaluated, not missing
Pangolin	Δ0.21	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 1.1	GERP 1.4
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,850 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00031% 5/1,612,738 alleles · very rare exomes 4/1,460,588 · genomes 1/152,150 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,713
Remaining individualsnot grpmax-eligible	0.0016%	62,446

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.Ser389Ter
Coding: c.1166C>G
MANE Select: NM_017952
Type: single nucleotide variant
Location: chr2:86130666 (GRCh38)
Gene constraint: LOEUF 1.132 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 86 PDB
Residue 389: an α-helix

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

Disease context

PTCD3-related disorder

Similar variants

PTCD3 c.1148-2A>G Likely pathogenic ★ same condition
PTCD3 p.Trp65Ter Likely pathogenic ★ same condition
PTCD3 c.654+4A>G Likely benign same condition
PTCD3 c.716+4T>G Likely benign same condition
PTCD3 p.Gly11Cys Likely benign same condition
PTCD3 p.Arg524Leu Uncertain significance ★★ ⚠ same type
PTCD3 p.Phe447Tyr Uncertain significance ★★ ⚠ same type
PTCD3 p.Pro138Leu Uncertain significance ★★ ⚠ same type

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-ser389ter (accessed [today's date]).

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