Is PDCD10 p.Met26Arg (c.77T>G) pathogenic?

PDCD10 p.Met26Arg (c.77T>G) is classified Uncertain significance in PDCD10 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-30). AlphaMissense: likely pathogenic (0.9891); Absent from gnomAD v4.1; Associated with cerebral cavernous malformation 3.

What condition is associated with PDCD10 p.Met26Arg (c.77T>G)?

PDCD10 p.Met26Arg (c.77T>G) is associated with cerebral cavernous malformation 3 (ClinVar).

How common is PDCD10 p.Met26Arg (c.77T>G) in the general population?

PDCD10 p.Met26Arg (c.77T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDCD10 p.Met26Arg (c.77T>G)?

AlphaMissense predicts likely pathogenic (score 0.9891) — an in-silico prediction, not a clinical call.

PDCD10 p.Met26Arg

c.77T>G · VCV4082049

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9891 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cerebral cavernous malformation 3

Computational evidence

Protein change
AlphaMissense	0.9891	likely pathogenic
REVEL	0.512	indeterminate
SaProt	LLR -11.51	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.46	donor gain · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 36 kb · p 3.1e-06 · regional, not allelic
Overall
CADD	31.0	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: PDCD10
Protein: p.Met26Arg
Coding: c.77T>G
MANE Select: NM_007217
Type: single nucleotide variant
Location: chr3:167720081 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 10 PDB
Residue 26: 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.Met26fs Likely pathogenic ★ 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-met26arg (accessed [today's date]).

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