Is PDCD10 p.Ala46= (c.138C>T) pathogenic?

PDCD10 p.Ala46= (c.138C>T) is classified Likely benign in PDCD10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-03). Ultra-rare (popmax 0.0332%, mid); Associated with Inborn genetic diseases.

What condition is associated with PDCD10 p.Ala46= (c.138C>T)?

PDCD10 p.Ala46= (c.138C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PDCD10 p.Ala46= (c.138C>T) in the general population?

PDCD10 p.Ala46= (c.138C>T) is ultra-rare (popmax 0.0332%, mid) (gnomAD).

PDCD10 p.Ala46=

c.138C>T · VCV4133550

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0332%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.019	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.27	GERP -4.7, phastCons 0.15
Overall
CADD	11.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0332% Middle Eastern · 2/6,030 alleles

Filtering AF 0.00585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.002% 29/1,452,452 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0332%	3,015
Remaining individualsnot grpmax-eligible	0.00805%	12,422
South Asian	0.0033%	30,289
European (non-Finnish)	0.00162%	61,673

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: PDCD10
Protein: p.Ala46=
Coding: c.138C>T
MANE Select: NM_007217
Type: single nucleotide variant
Location: chr3:167704854 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 10 PDB
Residue 46: an α-helix

Full PDCD10 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

PDCD10 p.Asn104Ser Uncertain significance ★★ ⚠ same condition
PDCD10 p.Leu44Arg Uncertain significance ★★ ⚠ same condition
PDCD10 p.Phe76Val Uncertain significance ★★ ⚠ same condition
PDCD10 p.Tyr27Cys Uncertain significance ★★ ⚠ same condition
PDCD10 p.Phe127= Likely benign ★★ same condition
PDCD10 p.Val72Leu Benign/Likely benign ★★ same condition
PDCD10 p.Asn156Lys Uncertain significance ★ ⚠ same condition
PDCD10 p.Asp133Ala 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/pdcd10-p-ala46 (accessed [today's date]).

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