Is PTCD3 p.Leu481Pro (c.1442T>C) pathogenic?

PTCD3 p.Leu481Pro (c.1442T>C) is classified Uncertain significance in PTCD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely pathogenic (0.96); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PTCD3 p.Leu481Pro (c.1442T>C)?

PTCD3 p.Leu481Pro (c.1442T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PTCD3 p.Leu481Pro (c.1442T>C) in the general population?

PTCD3 p.Leu481Pro (c.1442T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTCD3 p.Leu481Pro (c.1442T>C)?

AlphaMissense predicts likely pathogenic (score 0.96) — an in-silico prediction, not a clinical call.

PTCD3 p.Leu481Pro

c.1442T>C · VCV3784557

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.96 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.96	likely pathogenic · top 1% in PTCD3
REVEL	0.503	indeterminate
SaProt	LLR -12.42	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 31 kb · p 0.15 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Leu481Pro
Coding: c.1442T>C
MANE Select: NM_017952
Type: single nucleotide variant
Location: chr2:86133246 (GRCh38)
Gene constraint: LOEUF 1.132 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 86 PDB
Residue 481: an α-helix

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-leu481pro (accessed [today's date]).

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