Is PDCD10 p.Val192Ile (c.574G>A) pathogenic?

PDCD10 p.Val192Ile (c.574G>A) is classified Conflicting classifications of pathogenicity in PDCD10 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0516); Ultra-rare (popmax 0.0854%, nfe); Associated with cerebral cavernous malformation 3.

What condition is associated with PDCD10 p.Val192Ile (c.574G>A)?

PDCD10 p.Val192Ile (c.574G>A) is associated with cerebral cavernous malformation 3 (ClinVar).

How common is PDCD10 p.Val192Ile (c.574G>A) in the general population?

PDCD10 p.Val192Ile (c.574G>A) is ultra-rare (popmax 0.0854%, nfe) (gnomAD).

What do computational predictors say about PDCD10 p.Val192Ile (c.574G>A)?

AlphaMissense predicts likely benign (score 0.0516) — an in-silico prediction, not a clinical call.

PDCD10 p.Val192Ile

c.574G>A · rs151267430 · VCV344108

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0516 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0854%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cerebral cavernous malformation 3

Computational evidence

Protein change
AlphaMissense	0.0516	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -0.043, phastCons 0.99
Regional constraint	o/e 0.71	unconstrained · MANE · 36 kb · p 3.1e-06 · regional, not allelic
Overall
CADD	15.63	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

Grpmax group 0.0854% European (non-Finnish) · 996/1,166,042 alleles

Filtering AF 0.081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0792%

Overall 0.0658% 1,051/1,597,720 alleles · ultra-rare exomes 979/1,446,112 · genomes 72/151,608 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0854%	1,171
Remaining individualsnot grpmax-eligible	0.0436%	2,293
African / African-American	0.0175%	5,724
Admixed American	0.0134%	7,484
South Asian	0.00551%	18,149
Finnishnot grpmax-eligible	0.00314%	31,838

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.Val192Ile
Coding: c.574G>A
MANE Select: NM_007217
dbSNP: rs151267430
Type: single nucleotide variant
Location: chr3:167684373 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 10 PDB
Residue 192: 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 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
PDCD10 p.Glu140Ter 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-val192ile (accessed [today's date]).

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