Is PTCD3 p.Phe335Cys (c.1004T>G) pathogenic?

PTCD3 p.Phe335Cys (c.1004T>G) is classified Uncertain significance in PTCD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: ambiguous (0.507); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PTCD3 p.Phe335Cys (c.1004T>G)?

PTCD3 p.Phe335Cys (c.1004T>G) is associated with Inborn genetic diseases (ClinVar).

How common is PTCD3 p.Phe335Cys (c.1004T>G) in the general population?

PTCD3 p.Phe335Cys (c.1004T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTCD3 p.Phe335Cys (c.1004T>G)?

AlphaMissense predicts ambiguous (score 0.507) — an in-silico prediction, not a clinical call.

PTCD3 p.Phe335Cys

c.1004T>G · VCV4146802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.507 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.507	ambiguous
REVEL	0.572	indeterminate
SaProt	LLR -8.99	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 31 kb · p 0.15 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

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.Phe335Cys
Coding: c.1004T>G
MANE Select: NM_017952
Type: single nucleotide variant
Location: chr2:86127213 (GRCh38)
Gene constraint: LOEUF 1.132 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 86 PDB
Residue 335: 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-phe335cys (accessed [today's date]).

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