Is PDCD10 p.Phe76= (c.228C>T) pathogenic?

PDCD10 p.Phe76= (c.228C>T) is classified Likely benign in PDCD10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-24). Very rare (popmax 0.00134%, afr); Associated with cerebral cavernous malformation 3.

What condition is associated with PDCD10 p.Phe76= (c.228C>T)?

PDCD10 p.Phe76= (c.228C>T) is associated with cerebral cavernous malformation 3 (ClinVar).

How common is PDCD10 p.Phe76= (c.228C>T) in the general population?

PDCD10 p.Phe76= (c.228C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

PDCD10 p.Phe76=

c.228C>T · rs377093246 · VCV1789077

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

cerebral cavernous malformation 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.116	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.7, phastCons 1
Overall
CADD	14.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,828 alleles

Filtering AF 0.000544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00043%

Overall 0.000808% 13/1,608,820 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,828
European (non-Finnish)	0.00102%	97,947

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.Phe76=
Coding: c.228C>T
MANE Select: NM_007217
dbSNP: rs377093246
Type: single nucleotide variant
Location: chr3:167697049 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 10 PDB
Residue 76: an α-helix

Full PDCD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cerebral cavernous malformation 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDCD10 p.Phe76Val Uncertain significance ★★ ⚠ same residue
PDCD10 c.396-2A>G Pathogenic ★★ same condition
PDCD10 c.474+5G>A Pathogenic/Likely pathogenic ★★ same condition
PDCD10 c.557+1G>A Pathogenic ★★ same condition
PDCD10 p.Arg108Ter Pathogenic ★★ same condition
PDCD10 p.Arg196Ter Pathogenic ★★ same condition
PDCD10 p.Arg35Ter Pathogenic ★★ same condition
PDCD10 p.Arg95Ter Pathogenic ★★ 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-phe76 (accessed [today's date]).

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