Is PDCD10 p.Val72Met (c.214G>A) pathogenic?

PDCD10 p.Val72Met (c.214G>A) is classified Uncertain significance in PDCD10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0886); Very rare (popmax 0.005%, amr); Associated with cerebral cavernous malformation 3.

What condition is associated with PDCD10 p.Val72Met (c.214G>A)?

PDCD10 p.Val72Met (c.214G>A) is associated with cerebral cavernous malformation 3 (ClinVar).

How common is PDCD10 p.Val72Met (c.214G>A) in the general population?

PDCD10 p.Val72Met (c.214G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about PDCD10 p.Val72Met (c.214G>A)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

PDCD10 p.Val72Met

c.214G>A · rs562763010 · VCV2035295

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

cerebral cavernous malformation 3

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.375	indeterminate
SaProt	LLR -6.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 36 kb · p 3.1e-06 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.005% Admixed American · 3/60,004 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00237%

Overall 0.00329% 53/1,611,758 alleles · very rare exomes 48/1,459,588 · genomes 5/152,170 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,001
Remaining individualsnot grpmax-eligible	0.00481%	20,802
European (non-Finnish)	0.00357%	28,049
African / African-American	0.00267%	37,441
South Asian	0.0022%	45,519
Finnishnot grpmax-eligible	0.00156%	63,940

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.Val72Met
Coding: c.214G>A
MANE Select: NM_007217
dbSNP: rs562763010
Type: single nucleotide variant
Location: chr3:167697063 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 10 PDB

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.Val72Leu Benign/Likely benign ★★ 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-val72met (accessed [today's date]).

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