Is PTCD3 p.Leu12= (c.36C>A) pathogenic?

PTCD3 p.Leu12= (c.36C>A) is classified Likely benign in PTCD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-01). Very rare (popmax 0.00667%, amr).

How common is PTCD3 p.Leu12= (c.36C>A) in the general population?

PTCD3 p.Leu12= (c.36C>A) is very rare (popmax 0.00667%, amr) (gnomAD).

PTCD3 p.Leu12=

c.36C>A · VCV4872509

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

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 -0.85	GERP -1
Overall
CADD	2.888	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,006 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000434% 7/1,613,626 alleles · very rare exomes 5/1,461,412 · genomes 2/152,214 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,002
Remaining individualsnot grpmax-eligible	0.0016%	62,438
European (non-Finnish)	0.000169%	589,995

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.Leu12=
Coding: c.36C>A
MANE Select: NM_017952
Type: single nucleotide variant
Location: chr2:86106283 (GRCh38)
Gene constraint: LOEUF 1.132 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 86 PDB

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

Similar variants

PTCD3 p.Leu12Phe Uncertain significance ★ ⚠ same residue
PTCD3 p.Arg524Leu Uncertain significance ★★ ⚠ same type
PTCD3 p.Phe447Tyr Uncertain significance ★★ ⚠ same type
PTCD3 p.Pro138Leu Uncertain significance ★★ ⚠ same type
PTCD3 p.Pro97Ser Uncertain significance ★★ ⚠ same type
PTCD3 c.1148-2A>G Likely pathogenic ★ same type
PTCD3 c.1630-1G>A Likely pathogenic ★ same type
PTCD3 c.1979+1G>A Likely pathogenic ★ 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-leu12 (accessed [today's date]).

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