Is PTCD3 p.Pro407Ser (c.1219C>T) pathogenic?

PTCD3 p.Pro407Ser (c.1219C>T) is classified Uncertain significance in PTCD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). AlphaMissense: likely benign (0.1217); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PTCD3 p.Pro407Ser (c.1219C>T)?

PTCD3 p.Pro407Ser (c.1219C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PTCD3 p.Pro407Ser (c.1219C>T) in the general population?

PTCD3 p.Pro407Ser (c.1219C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTCD3 p.Pro407Ser (c.1219C>T)?

AlphaMissense predicts likely benign (score 0.1217) — an in-silico prediction, not a clinical call.

PTCD3 p.Pro407Ser

c.1219C>T · VCV3427176

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1217 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1217	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -6.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP -1.8, phastCons 0.027
Regional constraint	o/e 1.05	unconstrained · MANE · 31 kb · p 0.15 · regional, not allelic
Overall
CADD	6.627	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PTCD3
Protein: p.Pro407Ser
Coding: c.1219C>T
MANE Select: NM_017952
Type: single nucleotide variant
Location: chr2:86130719 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTCD3 p.Arg524Leu Uncertain significance ★★ ⚠ same condition
PTCD3 p.Pro138Leu Uncertain significance ★★ ⚠ same condition
PTCD3 p.Pro97Ser Uncertain significance ★★ ⚠ same condition
PTCD3 p.Ala109Ser Uncertain significance ★ ⚠ same condition
PTCD3 p.Ala362Ser Uncertain significance ★ ⚠ same condition
PTCD3 p.Ala499Pro Uncertain significance ★ ⚠ same condition
PTCD3 p.Ala568Pro Uncertain significance ★ ⚠ same condition
PTCD3 p.Ala6Val 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-pro407ser (accessed [today's date]).

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